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Article

MicroRNA Alterations Induced in Human Skin by Diesel Fumes, Ozone, and UV Radiation

1
Animal Science Department, Plants for Human Health Institute, North Carolina State University, Research Campus Kannapolis, Kannapolis, NC 28081, USA
2
Department of Environmental Sciences and Prevention, University of Ferrara, 44121 Ferrara, Italy
3
Department of Food and Nutrition, Kyung Hee University, Seoul 130-701, Korea
4
Lung Cancer Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy
5
Department of Health Sciences, University of Genova, 16132 Genova, Italy
6
Department of Experimental Medicine, University of Genova, 16132 Genova, Italy
7
UOC Mutagenesis and Cancer Prevention, IRCCS San Martino Hospital, 16132 Genova, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: David Alan Rizzieri
J. Pers. Med. 2022, 12(2), 176; https://doi.org/10.3390/jpm12020176
Received: 6 October 2021 / Revised: 21 January 2022 / Accepted: 24 January 2022 / Published: 28 January 2022
(This article belongs to the Special Issue Role of MicroRNA in Cancer Development and Treatment)

Abstract

Epigenetic alterations are a driving force of the carcinogenesis process. MicroRNAs play a role in silencing mutated oncogenes, thus defending the cell against the adverse consequences of genotoxic damages induced by environmental pollutants. These processes have been well investigated in lungs; however, although skin is directly exposed to a great variety of environmental pollutants, more research is needed to better understand the effect on cutaneous tissue. Therefore, we investigated microRNA alteration in human skin biopsies exposed to diesel fumes, ozone, and UV light for over 24 h of exposure. UV and ozone-induced microRNA alteration right after exposure, while the peak of their deregulations induced by diesel fumes was reached only at the end of the 24 h. Diesel fumes mainly altered microRNAs involved in the carcinogenesis process, ozone in apoptosis, and UV in DNA repair. Accordingly, each tested pollutant induced a specific pattern of microRNA alteration in skin related to the intrinsic mechanisms activated by the specific pollutant. These alterations, over a short time basis, reflect adaptive events aimed at defending the tissue against damages. Conversely, whenever environmental exposure lasts for a long time, the irreversible alteration of the microRNA machinery results in epigenetic damage contributing to the pathogenesis of inflammation, dysplasia, and cancer induced by environmental pollutants.
Keywords: microRNAs; environmental risk factors; cutaneous tissues; ozone exposure microRNAs; environmental risk factors; cutaneous tissues; ozone exposure

1. Introduction

The World Health Organization (WHO) estimated that circa 90% of the global urban population lives with pollutant levels exceeding WHO guideline limits. This has been linked to the premature death of seven million people each year [1]. The target organs of pollution include the lungs, gut, brain, and mainly the skin [2].
The skin is the largest sensory organ (approximately 2 m2) in our body and is composed of two main layers: the epidermis and the dermis. The dermis is mainly formed of fibroblasts involved in the secretion of elastin and collagen fibers, embedded with nerve endings, sebaceous glands, hair follicles, and blood and lymphatic vessels. During the process of differentiation/keratinization, keratinocytes withdraw from the cell cycle and begin to express differentiation-dependent markers (i.e., keratins), eventually becoming anucleated densely keratinized corneocytes [3]. These cells are held together in the multilayered stratum corneum by a lipid-laden extracellular matrix (ECM), which performs the barrier function of the skin [4]. Recently, it has been demonstrated that the skin is not an impenetrable tissue, and it can even be a gateway for certain pollutants, even affecting internal organs [5].
The use of the word “pollution” can be misleading given that there are several different pollutants that can affect our health. Based on their chemical and physical properties as well as their sources, The United States Environmental Protection Agency (EPA) has identified the most common air pollutants, also known as “criteria air pollutants”, as ozone (O3), particulate matter (PM), carbon monoxide (CO), lead, sulfur dioxide (SO2), and nitrogen dioxide (NO2) [6]. Clear evidence of the correlation between each pollutant and skin disorder has not yet been established; however, the harmful effects of O3, PM, and UV radiation have been well demonstrated. To date, only a few studies have compared the cutaneous effect of different pollutant exposure. Several skin diseases such as atopic dermatitis (AD), psoriasis, acne, and, in some cases, also skin cancer have been linked, either directly or indirectly, to pollution exposure, although the debate is still open. In particular, exposure to O3 and PM have been demonstrated to be associated with skin aging, including wrinkle formation and dark spots, respectively [7]. In addition, the study by Xu et al. [8] demonstrated the association between ozone exposure and cutaneous conditions by analyzing the emergency room (ER) visits for skin conditions together with the levels of several air pollutants such as O3, PM10, SO2, and NO2. The authors were able to extrapolate that skin conditions such as urticaria, eczema, contact dermatitis, rash/other non-specific eruptions, and infected skin diseases were exacerbated by exposure to increased ozone levels. Another more recent publication has further examined the association of short-term changes in air quality with emergency department (ED) visits for urticaria in Canada. A total of 2905 ED visits were analyzed, and a positive and significant correlation was observed between air quality levels and ED visits for urticaria, confirming that air pollution can affect skin physiology [9,10].
O3 and PM have quite different mechanisms of action, while O3 is not able to penetrate the skin and reacts directly with the lipids present in the stratum corneum, PM can possibly enter the skin via the hair follicles or enable the skin to absorb components present in the PM (such as polycyclic aromatic hydrocarbons—PAH) and lead to an epidermal OxInflammatory reaction [11,12].
Indeed, it is now well established that ozone and diesel particles, together with UV radiation, can induce a proinflammatory response in parallel to an altered tissue redox homeostasis [13].
In addition to the ability of pollution to produce oxidative and inflammatory mediators, recent studies have indicated that DNA methylation patterns can be greatly influenced by environmental factors such as ambient air pollution, and these epigenetic changes are linked with diverse diseases [14,15,16].
In fact, several reports have shown that epigenetic alterations could be an important pathway through which environmental factors exert their effects [14,17]. Epigenetic refers to the alterations in gene expression levels that occur without changes in the underlying DNA sequence (such as DNA methylation, histone modification, miRNA, and noncoding RNA expression [18,19]). It should be mentioned that several pathologies, including cancers, have been associated with epigenetic modifications [18]. Exposure to environmental stimuli may result in epigenetic changes, which can impact gene expression and predisposition to developing pathological conditions. [20]. Understanding epigenetic alterations due to exposure to specific pollutants may lead to the development of biomarkers to assess the disease risk associated with air pollution. Micro-RNAs and noncoding RNAs (ncRNAs) play critical roles in gene expression and contribute to epigenetic control in the process [21]. For this reason, the present study aimed to evaluate the different miRNA epigenetic patterns related to the specific exposure of cutaneous tissues to pollutants such as ozone, diesel exhaust, and to the stressor UV radiation, which is the most toxic and most present in urban areas.

2. Materials and Methods

2.1. Ex Vivo Human Skin Explants Preparation

Human skin biopsies (12 mm diameter) were obtained from three healthy Caucasian donors (40–45 years old) who underwent elective abdominoplasties at Hunstad/Kortesis/Bharti Cosmetic Surgery clinic. In total, 24 punch biopsies were taken from the abdominal skin of each donor, and subcutaneous fat was removed with sterile scissors and a scalpel.
The biopsies, comprising dermal and epidermal layers, were rapidly rinsed with Phosphate-Buffered Saline (PBS, Gibco, New York, NY, USA). The biopsies were then moved into 6-well dishes containing 2 mL of complete Dulbecco’s Modified Eagle Medium (DMEM) with 10% Fetal Bovine Serum (FBS) and 1% of antibiotics and antimycotics (100 U/mL penicillin and 100 µg/mL, Gibco, New York, NY, USA) added; then, they were incubated at 37 °C in 5% CO2 for overnight recovery.
The following day the medium was replaced with a fresh one, and the biopsies were exposed to the different pollutants as discussed below.
The experiment was performed at least in triplicate for each condition and donor.

2.2. Ex Vivo Human Skin Explants Ozone (O3) Exposure

A full 24 h after skin biopsy collection, ex vivo explants were allocated into a plexiglass sealed chamber, connected to the ozone generator machine (ECO3 model CUV-01, Model 306 Ozone Calibration Source, 2B Technologies, Ozone solution, ITA), and exposed to 0.2 ppm for 4 h. Sample biopsies were then collected following ozone exposure (T0) or after 24 h (T24).

2.3. Ex Vivo Human Skin Explants Diesel Engine Exhaust (Diesel) Exposure

Another set of skin biopsies was exposed to diesel engine exhaust by letting the engine run for 10 s and allowing the exhaust to reach the sealed exposure chamber where the skin biopsies remained for 30 min. Specifically, the skin explants were placed into a sealed plexiglass box connected to a Kubota RTV-X900 diesel engine (3-cylinder, 4-cycle diesel with overhead valves, 1123 cc with 24.8 HP at 3000 rpm). After the 30 min of Diesel exposure, the exposure medium was changed with a fresh one, and the biopsies were either collected (T0) or moved back into the incubator at 37 °C in 5% CO2 for 24 h (T24).

2.4. Ex Vivo Human Skin Explants Ultraviolet Light (UV) Exposure

The other human skin biopsies were exposed to 200 milli Joule (mJ) UVA/UVB light, which equates to circa 2 h at solar apex and corresponding to 10 minimal erythemal doses (MED, 1 MED = 20 mJ/cm2) [22]. UVA/UVB light (exposure of circa 20 s) was generated by a Sol1A Class ABB Solar Simulator, equipped with a xenon lamp (Newport Oriel Sol1A, CA, USA). Samples were collected after UV exposure (T0), or after 24 h (T24).
To match the real solar spectrum at the condition of the sun at the Zenith angle of 0, we performed UV exposure with a UVA/UVB ratio of 21:1 measured with a radiometer ILT2400 Hang-Held Light Meter/Optometer (International Light Technologies, Inc., Peabody, MA, USA).

2.5. Total RNA Extraction and Lyophilization

Total RNA extraction was performed using a miRNeasy Mini kit QIAGEN (Hilgen, DE, cat. 1038703) and Qiazol Lysis Reagent 50 QIAGEN (Hilgen, DE, cat. 1023537), according to the manufacturer’s protocol. Briefly, skin biopsies were homogenized in 700 µL of Qiazol Lysis Reagent, with a tissue homogenizer (Precellys 24 homogenizer, 5 cycles 6500 rpm 3 × 30 s, at 4 °C). Samples were then centrifuged (12,700 rpm, 5 min at 4 °C), the supernatant was collected and transferred to a new tube containing 140 µL of Chloroform, and then centrifuged again (12,000 g, 15 min at 4 °C). The upper aqueous phase was transferred to a new tube containing 1.5 volumes of ethanol 100% and mixed thoroughly. Then, half of the volume was moved into the RNeasy Mini spin column and centrifuged (8000× g, 30 s, RT). This last step was repeated for the other half of the volume. Next, 700 µL of diluter Buffer RWT was added to the column, centrifuged (8000× g, 30 s, RT), and then the liquid was discarded. Next, the addition of 500 µL of diluted Buffer RPE to the column, centrifugation (8000× g, 30 s, RT), and discarding of the liquid was repeated twice. Finally, the columns were moved into new Rnase free tubes, centrifuged at maximum speed for 1 min, and 30 µL of RNase free water was added to the spin column membrane. Elution of RNA was performed by centrifugation at 8000 g, 1 min, RT.
Then, the eluted RNA was concentrated via a lyophilization process (1.5 h, Low Setting, RT) using a Savant DNA SpeedVac Concentrator (Savant DNA120, DNA 120 OP, Thermo Electron Corporation, Waltham, MA, USA).

2.6. miRNA-Microarray and Bioinformatic Analyses

miRNA expression profiling was carried out by an Agilent platform, following the miRNA Microarray protocol v.3.1.1 (Agilent Technologies, Santa Clara, CA, USA). Briefly, 50 ng of total RNA containing miRNAs and Spike-in controls underwent dephosphorylation and a labeling step with Cyanine 3-pCp. The Cy3-labeled RNA was then purified using Micro Bio-Spin P-6 Gel Column (Bio-Rad Laboratories, Inc., Hercules, CA, USA) and hybridized on a Human miRNA microarray slide 8 × 60K (Agilent Technologies; including 2549 miRNAs, miRBase 21.0) at 55 °C for 20 h. After washing, the slides were scanned by a G2565CA scanner (Agilent Technologies), and the images were extracted by Feature Extraction software v.10 (Agilent Technologies). Microarray raw data were deposited in the Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo); GEO number accession requested, 15 March 2022).
Bioinformatic analyses were performed using the GeneSpring software (GeneSpring Multi-Omic Analysis v 14.9 by Agilent Technologies). For each sample, the intensities of replicated spots on each array were log transformed and averaged. Data processing was performed by 3D principal component analysis (PCA) scores and Hierarchical Clustering.
Comparisons between sets of data were performed by evaluating the fold changes. A volcano Plot T-Test analysis for all miRNA entities was run, using Fold Change ≥2 and p-value ≤ 0.05. Because log transformed data were used, negative and zero signals were transformed into 0.01 values. This approach could result in artificially high-fold variations. To correct this artifact, we now report in Tables that fold variation values upregulated more than 10 times into ‘>10-fold’ and fold variation values downregulated more than 10 times into <0.1-fold.
miRNAs related to three different environmental exposures (Environmental Exposure miRNA Signature) were determined by analyzing miRNAs comparatively in exposed vs. non-exposed subjects. Environmental exposures were determined for each sample according to (a) Diesel, (b) Ozone, and (c) UV.
To understand the relationship between environmental exposure signatures and their biological significance in human tissues, a target detection for each environmental exposure signature was performed using the TargetScan prediction database.

3. Results

Comparison of miRNA Expression Profile between Pollutants

The overall trend of miRNA expression in human skin either untreated or exposed to diesel, ozone, and UV was evaluated at 0 and 24 h by Line plot analysis. (Figure 1).
The expression line plot was similar at 0 and 24 h in unexposed skin. Diesel induced dramatic alteration of miRNA profile compared to air but mainly after 24 h. Conversely, miRNA alteration induced by ozone was remarkable at time 0 while being much more attenuated compared to untreated skin at 24 h. miRNA profiles were slightly increased by UV exposure, mostly at 24 h compared to unexposed skin.
Scatter plot analyses were performed to assess the number of miRNAs with more than two-fold profile alteration compared to untreated (air-exposed), Figure 2.
Each miRNA is represented by colored dots, whose expression intensity can be inferred from the position on the horizontal and vertical axes. The horizontal axis indicates the miRNA expression level in untreated samples and the vertical axis in treated (diesel, ozone, and UV) samples. The central diagonal lines indicate the equivalence (<two-fold variation) in the intensity of miRNA expression in treated as compared to untreated samples. miRNA dots falling outside the green diagonal lines indicate higher than two-fold differences in miRNA expression between the tested experimental conditions. Scatter plot analyses compared untreated (air) and treated (diesel, ozone, and UV) samples both at 0 and 24 h. miRNA colors reflect the signal intensity in the treated samples (red is high, yellow is intermediate, and blue is low). Upregulated miRNAs are located in the upper-right area, and downregulated miRNAs are in the lower-right area of the scatter plots.
For diesel and to a lesser extent for UV, a cloud of downregulated miRNAs was detected already at 0 h, while the additional cloud of upregulated miRNAs was detected only at 24 h.
Conversely, for ozone, two clouds of both upregulated and downregulated miRNAs were already detected at time 0.
At time 0, out of the 2549 miRNAs tested, 100 (2.5%) were downregulated (blue dots) while 122 (4.8%) were upregulated (red dots) after exposure to diesel. Immediately after ozone exposure, we evidenced 262 (10.3%) downregulated miRNAs and 297 (11.6%) upregulated; however, upon UV exposure, we detected that 238 (9.3%) were downregulated and 294 (11.5%) upregulated.
At 24 h, out of the 2549 miRNAs tested, 219 (8.6%) were downregulated (blue dots), and 251 (9.8%) were upregulated (red dots) after exposure to diesel; 229 (8.9%) were downregulated, and 238 (9.3%) upregulated after ozone exposure; and 174 (6.8%) were downregulated and 241 (9.4%) upregulated after UV exposure.
The effects of the tested pollutants on the whole miRNA expression profile were compared by unsupervised principal component analysis of variance (PCA) and supervised hierarchical cluster (HCA) analyses.
The PCA at 0 h (Figure 3) showed that the miRNA profiles of ozone and UV treated samples were remarkably altered, being located far away and in another quadrant, as compared to the untreated (air) samples. Conversely, the miRNA profile in diesel-treated samples was only slightly distant from the untreated samples, being located in the same quadrant.
The PCA at 24 h (Figure 3) reported that the miRNA profiles of all pollutant-treated samples (including diesel) were located far away and in another quadrant compared to the untreated sample. The samples treated with diesel and ozone were close to each other but far away from the UV-treated sample. This finding indicates that the pattern of miRNAs altered by UV is quite different from those induced by ozone and diesel exposure. This situation is likely due to the different pathogenic mechanisms induced by exciting radiation (UV) as compared to gaseous (ozone) and mixed gaseous-particulate pollutants (diesel).
The HCA at 0 h (Figure 4) showed that the most remarkable alterations in miRNA profiles were induced by ozone, whose expression profile was located at the right of the hierarchical tree far away from the untreated (air) sample. An intermediate situation occurred for UV, whose alteration profile was in the central part of the hierarchical tree. miRNA alterations induced by diesel were less remarkable; indeed, the profile was linked to the untreated (air) sample in the hierarchical tree.
The HCA at 24 h (Figure 4) indicated that the most remarkable alterations in miRNA profiles were induced by diesel, whose expression profile was located at the right of the hierarchical tree far away from the untreated (air) sample. An intermediate response was visible for UV, whose alteration profile was located in the central part of the hierarchical tree. On the other hand, the changes in miRNA profiles induced by ozone exposure were less remarkable; in fact, this profile was linked to the untreated (air) sample in the hierarchical tree.
A Venn diagram data representation was used to identify microRNAs presented in both lists, i.e., altered by each pollutant both at 0 and 24 h.
These miRNAs represent the specific miRNA signature induced by each pollutant. Their identity is reported in Table 1 (diesel), Table 2 (ozone), and Table 3 (UV). These Tables enlist miRNAs modulating their expression more than two-fold and above the statistical significance threshold of p < 0.05 considering the four replicates spotted in each microarray. A comparison of fold variation was made by dividing the signal intensity detected in treated skin by those detected in untreated skin. Fold variation values >2.0 indicate upregulation after treatment and <0.5 downregulation after treatment. Available information for the main biological pathways regulated by modulated microRNAs is also reported (column Function), as well as the reference from where this information was collected.
MicroRNAs reported in Table 1, Table 2 and Table 3 were selected by both volcano plot analysis and Venn diagram data representation. These miRNAs represent the specific signature of each pollutant, being modulated both after short-term exposure (UV 20 s, diesel 30 min, and ozone 4 h) and long-term exposure (24 h for all pollutants).
Fold variations reported in Table 1, Table 2 and Table 3 are the rate of signal intensity changes between treated and untreated samples at 24 h.
The main biological pathways regulated by these miRNAs, as inferred from available literature, are also reported.
The main pathways targeted by tested pollutants were: apoptosis, cell cycle, and inflammation (Table 4).

4. Discussion and Conclusions

The constant exposure to oxidants, including ultraviolet (UV) radiation and other environmental pollutants, such as diesel fuel exhaust and ozone, makes the skin our first defense against the outdoor environment, and it is also the tissue more affected by outdoor stressors. The contribution of the now defined “exposome” to extrinsic skin aging and skin conditions is well accepted. Pollution is one of the main players included in the skin exposome [224]. It has been recently shown [285] that exposure to more pollutants can have an additive effect. This could be a consequence of the different mechanisms of action of each stressor based on its chemical/physical properties.
It is generally understood that the toxic effects of O3, although it is not a radical species, per se, are mediated through free radical reactions either directly by the oxidation of biomolecules to give classical radical species (hydroxyl radical) or by driving the radical-dependent production of cytotoxic nonradical species (aldehydes) [286].
O3 cannot penetrate the SC, so it first interacts with the lipids present in the outermost layer of the skin, leading to the generation of a number of bioreactive species [287]. It can be suggested that reaction with the well-organized interstitial lipids and protein constituents of the outermost stratum corneum barrier, and the diffusion of bioreactive products from this tissue into the viable layers of the epidermis, may represent a contribution to the development/exacerbation of skin disorders associated with O3 exposure. Indeed, once these “mediators” can reach live cells (keratinocytes, fibroblasts, etc.), they can induce a cellular defensive and inflammatory response that leads to an inflammatory/oxidative vicious cycle, called OxInflammation [288]. Unless quenched by endogenous or exogenous mechanisms, this will damage the skin and compromise its barrier functions, contributing to extrinsic skin aging.
Different hypotheses have been proposed concerning the initiation of the PM’s detrimental effects on cutaneous tissues. This could be due to an indirect effect by an outside-inside signaling cascade. PM, especially smaller particles, may carry metal ions and/or organic compounds such as polycyclic aromatic hydrocarbons (PAHs), which are highly lipophilic and can penetrate the skin surface [287]. This is in agreement with our observations. Moreover, PAHs are potent ligands for the AhR receptor, expressed by both keratinocytes and melanocytes, which upregulates proinflammatory mediators and increases ROS production [289].
In a previous study, we provided evidence that PM develops cutaneous damage not only directly once particles reach deeper layers in the epidermis but also indirectly by triggering a signaling pathway [290]. Oxidative stress and an inflammatory response seem to be important steps in the PM toxic mechanisms.
The solar spectrum reaching the surface of the earth is divided into three main segments based on wavelength: UVC (100−290 nm), UVB (290−320 nm), and UVA (320−400 nm). Both UVA and UVB have acute and chronic effects on human skin [287]. It has been established that approximately 50% of UV-induced direct cellular injury accounts for the remainder of the damage [291,292,293].
Therefore, although UV, PM, and ozone have different mechanisms of action, they all have the common denominator of damage that can be summarized as oxidative stress.
This effect is not limited to a biochemical effect, but it has been shown that air pollutants modulate epigenetic states, ranging from DNA methylation to miRNAs expression [294].
The aim of this study was to evaluate the different miRNA cutaneous responses to the main pollutants to which our skin is exposed daily.
It was not surprising that there was a clear difference among the pollutants in terms of the modulated miRNAs and the pathways associated with the epigenetic variation.
We found that the main pathways affected by the analyzed pollutants were: apoptosis, cell cycle, inflammation, DNA repair, and cancer. Of note, apoptosis was not associated with O3 exposure, and this could be a consequence of the O3 mechanism of action, which leads to the generation of proinflammatory mediators (H2O2 and aldehydes) less aggressively compared to UV and PM [89,100]
The ability of UV to induce DNA damage and subsequent apoptosis has been well demonstrated in the past, and our data confirm these results under the epigenetic mechanism as well. In addition, our data confirmed the involvement of O3 exposure in cutaneous inflammation, as previously demonstrated by Xu et al., where ER visit for skin inflammatory conditions perfectly correlated with increased ozone levels in urban cities [17,20].
To confirm that the O3 epigenetic effect is tissue-specific (due to the different mediators generated by the interaction with different tissues), the work by [295] showed that the expression analysis of sputum samples revealed that O3 exposure significantly increased the expression levels of several miRNAs, namely miR-132, miR-143, miR-145, miR-199b-5p, miR-222, miR-223, miR-25, miR-424, and miR-582-5p that while not detected in our analysis were still involved in inflammation. A quite recent work suggests that the main effect of PM on the skin is due to the absorption of PAHs, which can lead to skin barrier perturbation and damage [296]. PAH exposure has been already associated with epigenetic variation related mainly to DNA methylation.
In the present study, we have shown for the first time that PAH (present in diesel particles) can affect cutaneous epigenetics related to miRNA expression, highlighting the possible detrimental effect that those compounds can have on the skin [61]. The time-related kinetic differences in miRNA expression at 0 and 24 h reflect the different nature of the tested pollutants.
Ozone is a volatile gas; accordingly, its interaction with the skin induces effects on a short–term basis because this gas is neither metabolized nor entrapped into skin layers. UV radiation induces short-term alteration triggering reactive mechanisms (DNA repair, etc.), requiring at least 8 h to be activated by the modulation of the microRNA machinery. MicroRNAs are highly sensitive to environmental stressors, as is well demonstrated in the lung for cigarette smoke [297] and airborne pollutants [298]. However, this issue has not yet been explored in the skin. The presented results herein provide experimental evidence that human skin undergoes dramatic changes in its physiological microRNA profile when exposed to environmental pollutants, either physical or chemical.
Diesel fumes are well known to induce genotoxic damage and DNA adduct formation [299], as well as microRNA alteration in the lung [300]. Diesel extracts can induce cancer in mouse skin [301]. The carcinogenic effect of diesel fumes is mainly due to the presence in this mixture of potent chemical genotoxic carcinogens such as nitropyrenes [302]. Indeed, epigenome regulation performed by the microRNA machinery can silence the expression of mutated oncogenes, thus defending our organism from the progression of the carcinogenic process. Only when genomic damage accumulates in the presence of irreversible alteration of the microRNA machinery does cancer occur [303].
Accordingly, the demonstration that microRNA are dramatically altered in human skin shows that diesel fumes are a complete skin carcinogen inducing both genomic and epigenomic alterations. The carcinogenicity of diesel fumes is exerted by the phase I and II metabolic reaction of its chemical components with particular reference to polycyclic aromatic hydrocarbons. This situation, together with the limited metabolic potential of the skin as compared to other tissues, explains why microRNA alterations reach the maximum level only after 40 h of exposure. The carcinogenicity of diesel fumes is confirmed by the finding that the majority (40%) of altered microRNA is involved in carcinogenesis processes, while only a minority is involved in defensive processes such as apoptosis (22%) and DNA repair (4%) [73,76].
Ozone displays an immediate effect on skin microRNA that does not increase after 24 h from the exposure. This finding indicates that adaptive mechanisms are triggered by ozone. Skin is well equipped with antioxidant defenses requiring some time to be activated. This situation is confirmed by the finding that the majority (31%) of altered microRNA is involved in defensive mechanisms allowing removal of damaged cells (apoptosis) and DNA repair (8%, i.e., two-fold more than diesel fumes), while only a minority in carcinogenesis (20%, i.e., two-fold less than diesel fumes).
UV radiation is carcinogenic, as demonstrated by the finding that this exposure induces the most dramatic alterations of microRNA involved in carcinogenesis (45%) compared to diesel fume and ozone.
Furthermore, UV displays a variety of other adverse biological effects, including cell loss by apoptosis, cell proliferation to replace lost cells, and inflammation. In this regard, microRNA alteration overlaps the main function of genes whose expression undergoes upregulation, as demonstrated in mouse skin [299].
Conversely, only a minority (7%) of microRNA involved in DNA repair are activated in human skin after 24 and 48 h. This situation is different from those reported in vivo in mouse skin after long-term exposure that activated a variety of genes involved in base excision (XP) and nucleotide excision (OGG1) DNA repair [304]. This finding indicates that only long-term exposure to UV is effective in activating defensive DNA repair, while exposures to high doses for a short time results in a lack of DNA repair activation. Because of this situation, sunburns, indicating the occurrence of UV exposure in the absence of effective activation of DNA and protein repair, represent a major risk factor for cancer development.
A limitation of the presented study is that skin biopsies were collected from three subjects only. Future studies using a wider number of subjects are necessary to explore the interindividual variation occurring in the miRNA of human skin when exposed to environmental pollutants.

5. Conclusions

In conclusion, our results provide experimental evidence in human skin that microRNA machinery is altered by exposure to environmental pollutants. This situation occurs regarding either chemical pollutants, such as diesel fumes and ozone, or exciting radiation, such as UV. MicroRNA alteration, on a short-term basis, represents an adaptive event triggering defensive mechanisms such as DNA repair and apoptosis, attenuating the consequences of molecular damage induced in the skin by environmental stressors. Whenever microRNA alterations persist for a long time because of continuous exposure to environmental stressors, microRNA defensive function is neutralized, thus leaving the pathology or even carcinogenesis process to develop. Our findings demonstrate that skin has potent microRNA machinery used to face exposure to environmental pollutants. The alteration induced in skin microRNA undergoes a signature specific to the environmental pollutant involved.

Author Contributions

Conceptualization, G.V. and A.I.; methodology A.P., S.C. and E.P. validation A.P. and A.I.; investigation G.V., resources, and data curation, and; writing—original draft preparation A.P., G.V. and A.I. and writing—review and editing all authors; visualization all authors, supervision A.I.; project administration, A.I. and G.V. and funding acquisition A.I. All authors have read and agreed to the published version of the manuscript.

Funding

This research was partially supported by the Italian Association for Cancer Research (AIRC, IG2017-20699 to A.I.).

Institutional Review Board Statement

Ethical review was waived for this study, due to the fact that human skin was obtained from cosmetic/elective surgery and was collected from consented donors under IRB approved protocols at facilities located in the continental United States.

Informed Consent Statement

As reported already in our recent Pambianchi E. et al., Antioxidants (Basel). 2021 Nov 30;10(12):1928, doi:10.3390/antiox10121928.

Data Availability Statement

The datasets used and/or analyzed during the current study are available in Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo); GEO number accession requested, 15 March 2022).

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Lelieveld, J.; Pozzer, A.; Pöschl, U.; Fnais, M.; Haines, A.; Münzel, T. Loss of life expectancy from air pollution compared to other risk factors: A worldwide perspective. Cardiovasc. Res. 2020, 116, 1910–1917. [Google Scholar] [CrossRef] [PubMed]
  2. World Health Organization (WHO). WHO’s Urban Ambient Air Pollution Database—Update 2016; WHO: Geneva, Switzerland, 2016. [Google Scholar]
  3. Fuchs, E. Epithelial Skin Biology. Three Decades of Developmental Biology, a Hundred Questions Answered and a Thousand New Ones to Address. Curr. Top. Dev. Biol. 2016, 116, 357–374. [Google Scholar] [CrossRef] [PubMed][Green Version]
  4. Feingold, K.R.; Schmuth, M.; Elias, P.M. The regulation of permeability barrier homeostasis. J. Investig. Dermatol. 2007, 127, 1574–1576. [Google Scholar] [CrossRef][Green Version]
  5. Valacchi, G.; Magnani, N.; Woodby, B.; Ferreira, S.M.; Evelson, P. Particulate Matter Induces Tissue OxInflammation: From Mechanism to Damage. Antioxid. Redox Signal. 2020, 33, 308–326. [Google Scholar] [CrossRef] [PubMed]
  6. Criteria Air Pollutants. Available online: https://www.epa.gov/criteria-air-pollutants (accessed on 30 September 2021).
  7. Fuks, K.B.; Hüls, A.; Sugiri, D.; Altug, H.; Vierkötter, A.; Abramson, M.J.; Goebel, J.; Wagner, G.G.; Demuth, I.; Krutmann, J.; et al. Tropospheric ozone and skin aging: Results from two German cohort studies. Environ. Int. 2019, 124, 139–144. [Google Scholar] [CrossRef]
  8. Xu, F.; Yan, S.; Wu, M.; Li, F.; Xu, X.; Song, W.; Zhao, J.; Xu, J.; Kan, H. Ambient ozone pollution as a risk factor for skin disorders. Br. J. Dermatol. 2011, 165, 224–225. [Google Scholar] [CrossRef]
  9. Kousha, T.; Valacchi, G. The air quality health index and emergency department visits for urticaria in Windsor, Canada. J. Toxicol. Environ. Health Part A Curr. Issues 2015, 78, 524–533. [Google Scholar] [CrossRef]
  10. Valacchi, G.; Porada, E.; Rowe, B.H. Ambient ozone and bacterium streptococcus: A link between cellulitis and pharyngitis. Int. J. Occup. Med. Environ. Health 2015, 28, 771–774. [Google Scholar] [CrossRef]
  11. Lademann, J.; Otberg, N.; Jacobi, U.; Hoffman, R.M.; Blume-Peytavi, U. Follicular penetration and targeting. J. Investig. Dermatol. Symp. Proc. 2005, 10, 301–303. [Google Scholar] [CrossRef][Green Version]
  12. Dijkhoff, I.M.; Drasler, B.; Karakocak, B.B.; Petri-Fink, A.; Valacchi, G.; Eeman, M.; Rothen-Rutishauser, B. Impact of airborne particulate matter on skin: A systematic review from epidemiology to in vitro studies. Part. Fibre Toxicol. 2020, 17, 35. [Google Scholar] [CrossRef]
  13. Ferrara, F.; Woodby, B.; Pecorelli, A.; Schiavone, M.L.; Pambianchi, E.; Messano, N.; Therrien, J.P.; Choudhary, H.; Valacchi, G. Additive effect of combined pollutants to UV induced skin OxInflammation damage. Evaluating the protective topical application of a cosmeceutical mixture formulation. Redox Biol. 2020, 34, 1014481. [Google Scholar] [CrossRef] [PubMed]
  14. Plusquin, M.; Guida, F.; Polidoro, S.; Vermeulen, R.; Raaschou-Nielsen, O.; Campanella, G.; Hoek, G.; Kyrtopoulos, S.A.; Georgiadis, P.; Naccarati, A.; et al. DNA methylation and exposure to ambient air pollution in two prospective cohorts. Environ. Int. 2017, 108, 127–136. [Google Scholar] [CrossRef] [PubMed]
  15. Ding, R.; Jin, Y.; Liu, X.; Zhu, Z.; Zhang, Y.; Wang, T.; Xu, Y. Characteristics of DNA methylation changes induced by traffic-related air pollution. Mutat. Res. Genet. Toxicol. Environ. Mutagen. 2016, 15, 46–53. [Google Scholar] [CrossRef] [PubMed]
  16. Xu, C.J.; Söderhäll, C.; Bustamante, M.; Baïz, N.; Gruzieva, O.; Gehring, U.; Mason, D.; Chatzi, L.; Basterrechea, M.; Llop, S.; et al. DNA methylation in childhood asthma: An epigenome-wide meta-analysis. Lancet Respir. Med. 2018, 6, 379–388. [Google Scholar] [CrossRef][Green Version]
  17. Alfano, R.; Herceg, Z.; Nawrot, T.S.; Chadeau-Hyam, M.; Ghantous, A.; Plusquin, M. The Impact of Air Pollution on Our Epigenome: How Far Is the Evidence? (A Systematic Review). Curr. Environ. Health Rep. 2018, 5, 544–578. [Google Scholar] [CrossRef]
  18. Weinhold, B. Epigenetics: The science of change. Environ. Health Perspect. 2006, 114, 160–167. [Google Scholar] [CrossRef][Green Version]
  19. Jin, B.; Li, Y.; Robertson, K.D. DNA methylation: Superior or subordinate in the epigenetic hierarchy? Genes Cancer 2011, 2, 607–617. [Google Scholar] [CrossRef][Green Version]
  20. Breton, C.V.; Marutani, A.N. Air Pollution and Epigenetics: Recent Findings. Curr. Environ. Health Rep. 2014, 1, 35–45. [Google Scholar] [CrossRef][Green Version]
  21. Chuang, J.C.; Jones, P.A. Epigenetics and microRNAs. Pediatr. Res. 2007, 61, 24–29. [Google Scholar] [CrossRef]
  22. Cancer, I.A. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, No. 100D.; World Health Organization: Geneva, Switzerland, 2012; Volume 100D, p. 341. ISBN 978-9283213215. [Google Scholar]
  23. Rooks, M.G.; Veiga, P.; Wardwell-Scott, L.H.; Tickle, T.; Segata, N.; Michaud, M.; Gallini, C.A.; Beal, C.; Van Hylckama-Vlieg, J.E.T.; Ballal, S.A.; et al. Gut microbiome composition and function in experimental colitis during active disease and treatment-induced remission. ISME J. 2014, 8, 1403–1417. [Google Scholar] [CrossRef]
  24. Guo, B.; Hui, Q.; Xu, Z.; Chang, P.; Tao, K. miR-495 inhibits the growth of fibroblasts in hypertrophic scars. Aging 2019, 11, 2898–2910. [Google Scholar] [CrossRef]
  25. Jun, H.; Ying, H.; Daiwen, C.; Bing, Y.; Xiangbing, M.; Ping, Z.; Jie, Y.; Zhiqing, H.; Junqiu, L. MIR-628, a microRNA that is induced by Toll-like receptor stimulation, regulates porcine innate immune responses. Sci. Rep. 2015, 5, 1–10. [Google Scholar] [CrossRef]
  26. Chen, H.; Ji, X.; She, F.; Gao, Y.; Tang, P. MIR-628-3p regulates osteoblast differentiation by targeting RUNX2: Possible role in atrophic non-union. Int. J. Mol. Med. 2017, 39, 279–286. [Google Scholar] [CrossRef] [PubMed][Green Version]
  27. Dong, P.; Xiong, Y.; Yue, J.; Xu, D.; Ihira, K.; Konno, Y.; Kobayashi, N.; Todo, Y.; Watari, H. Long noncoding RNA NEAT1 drives aggressive endometrial cancer progression via miR-361-regulated networks involving STAT3 and tumor microenvironment-related genes. J. Exp. Clin. Cancer Res. 2019, 8, 38–295. [Google Scholar] [CrossRef] [PubMed][Green Version]
  28. Zhang, T.; Cai, X.; Li, Q.; Xue, P.; Chen, Z.; Dong, X.; Xue, Y. Hsa-miR-875-5p exerts tumor suppressor function through down-regulation of EGFR in colorectal carcinoma (CRC). Oncotarget 2016, 7, 42225–42240. [Google Scholar] [CrossRef][Green Version]
  29. Kang, N.; Ou, Y.; Wang, G.; Chen, J.; Li, D.; Zhan, Q. miR-875-5p exerts tumor-promoting function via down-regulation of CAPZA1 in esophageal squamous cell carcinoma. PeerJ 2021, 9, e10020. [Google Scholar] [CrossRef]
  30. Liang, J.-J.; Wang, J.-Y.; Zhang, T.-J.; An, G.-S.; Ni, J.-H.; Li, S.-Y.; Jia, H.-T. MiR-509-3-5p-NONHSAT112228.2 Axis Regulates p21 and Suppresses Proliferation and Migration of Lung Cancer Cells. Curr. Top. Med. Chem. 2020, 20, 835–846. [Google Scholar] [CrossRef]
  31. Ram Kumar, R.M.; Boro, A.; Fuchs, B. Involvement and Clinical Aspects of MicroRNA in Osteosarcoma. Int. J. Mol. Sci. 2016, 17, 877. [Google Scholar] [CrossRef][Green Version]
  32. Yang, H.; Ren, J.; Bai, Y.; Jiang, J.; Xiao, S. Microrna-518-3p suppresses cell proliferation, invasiveness, and migration in colorectal cancer via targeting trip4. Biochem. Cell Biol. 2020, 98, 575–582. [Google Scholar] [CrossRef]
  33. Zhao, Y.; Lukiw, W.J. Bacteroidetes Neurotoxins and Inflammatory Neurodegeneration. Mol. Neurobiol. 2018, 55, 9100–9107. [Google Scholar] [CrossRef]
  34. Lu, L.; Zhang, H.; Dong, W.; Peng, W.; Yang, J. MiR-381 negatively regulates cardiomyocyte survival by suppressing Notch signaling. Vitr. Cell. Dev. Biol. Anim. 2018, 54, 610–619. [Google Scholar] [CrossRef]
  35. Reddy, S.D.N.; Pakala, S.B.; Ohshiro, K.; Rayala, S.K.; Kumar, R. MicroRNA-661, a c/EBPα target, inhibits metastatic tumor antigen 1 and regulates its functions. Cancer Res. 2009, 69, 5639–5642. [Google Scholar] [CrossRef] [PubMed][Green Version]
  36. Yonemori, K.; Seki, N.; Idichi, T.; Kurahara, H.; Osako, Y.; Koshizuka, K.; Arai, T.; Okato, A.; Kita, Y.; Arigami, T.; et al. The microRNA expression signature of pancreatic ductal adenocarcinoma by RNA sequencing: Anti-tumour functions of the microRNA-216 cluster. Oncotarget 2017, 8, 70097–70115. [Google Scholar] [CrossRef] [PubMed][Green Version]
  37. Son, G.H.; Kim, Y.; Lee, J.J.; Lee, K.Y.; Ham, H.; Song, J.E.; Park, S.T.; Kim, Y.H. MicroRNA-548 regulates high mobility group box 1 expression in patients with preterm birth and chorioamnionitis. Sci. Rep. 2019, 9, 19746. [Google Scholar] [CrossRef] [PubMed]
  38. Treiber, T.; Treiber, N.; Meister, G. Regulation of microRNA biogenesis and its crosstalk with other cellular pathways. Nat. Rev. Mol. Cell Biol. 2019, 20, 5–20. [Google Scholar] [CrossRef] [PubMed]
  39. Wu, Z.H.; Huang, K.H.; Liu, K.; Wang, G.T.; Sun, Q. DGCR5 induces osteogenic differentiation by up-regulating Runx2 through miR-30d-5p. Biochem. Biophys. Res. Commun. 2018, 505, 426–431. [Google Scholar] [CrossRef] [PubMed]
  40. Xu, Y.; Wu, D.; Jiang, Z.; Zhang, Y.; Wang, S.; Ma, Z.; Hui, B.; Wang, J.; Qian, W.; Ge, Z.; et al. MiR-616-3p modulates cell proliferation and migration through targeting tissue factor pathway inhibitor 2 in preeclampsia. Cell Prolif. 2018, 51, e12490. [Google Scholar] [CrossRef][Green Version]
  41. Ntoumou, E.; Tzetis, M.; Braoudaki, M.; Lambrou, G.; Poulou, M.; Malizos, K.; Stefanou, N.; Anastasopoulou, L.; Tsezou, A. Serum microRNA array analysis identifies miR-140-3p, miR-33b-3p and miR-671-3p as potential osteoarthritis biomarkers involved in metabolic processes. Clin. Epigenetics 2017, 12, 9–127. [Google Scholar] [CrossRef][Green Version]
  42. Sun, S.; Su, C.; Zhu, Y.; Li, H.; Liu, N.; Xu, T.; Sun, C.; Lv, Y. MicroRNA-544a Regulates Migration and Invasion in Colorectal Cancer Cells via Regulation of Homeobox A10. Dig. Dis. Sci. 2016, 61, 2535–2544. [Google Scholar] [CrossRef]
  43. Shin, C.-H.; Byun, J.; Lee, K.; Kim, B.; Noh, Y.K.; Tran, N.L.; Park, K.; Kim, S.-H.; Kim, T.H.; Oh, S.J. Exosomal miRNA-19a and miRNA-614 Induced by Air Pollutants Promote Proinflammatory M1 Macrophage Polarization via Regulation of RORα Expression in Human Respiratory Mucosal Microenvironment. J. Immunol. 2020, 205, 3179–3190. [Google Scholar] [CrossRef]
  44. Xiong, G.; Zhang, J.; Zhang, Y.; Pang, X.; Wang, B.; Zhang, Y. Circular RNA_0074027 participates in cell proliferation, apoptosis and metastasis of colorectal cancer cells through regulation of miR-525-3p. Mol. Med. Rep. 2021, 23, 324. [Google Scholar] [CrossRef] [PubMed]
  45. Templin, C.; Volkmann, J.; Emmert, M.Y.; Mocharla, P.; Müller, M.; Kraenkel, N.; Ghadri, J.R.; Meyer, M.; Styp-Rekowska, B.; Briand, S.; et al. Increased proangiogenic activity of mobilized CD34 + progenitor cells of patients with acute ST-segment-elevation myocardial infarction: Role of differential MicroRNA-378 expression. Arterioscler. Thromb. Vasc. Biol. 2017, 37, 341–349. [Google Scholar] [CrossRef][Green Version]
  46. Wang, H.; Chen, X.; Yang, B.; Xia, Z.; Chen, Q. MiR-924 as a tumor suppressor inhibits non-small cell lung cancer by inhibiting RHBDD1/Wnt/β-catenin signaling pathway. Cancer Cell Int. 2020, 8, 20–49. [Google Scholar] [CrossRef] [PubMed]
  47. Wang, X.; Tan, Y.; Xu, B.; Lu, L.; Zhao, M.; Ma, J.; Liang, H.; Liu, J.; Yu, S. GPR30 Attenuates Myocardial Fibrosis in Diabetic Ovariectomized Female Rats: Role of iNOS Signaling. DNA Cell Biol. 2018, 37, 821–830. [Google Scholar] [CrossRef] [PubMed]
  48. Shuai, F.; Wang, B.; Dong, S. MiR-522-3p promotes tumorigenesis in human colorectal cancer via targeting bloom syndrome protein. Oncol. Res. 2018, 26, 1113–1121. [Google Scholar] [CrossRef]
  49. Vettori, A.; Pompucci, G.; Paolini, B.; Del Ciondolo, I.; Bressan, S.; Dundar, M.; Kenanoğlu, S.; Unfer, V.; Bertelli, M. Genetic background, nutrition and obesity: A review. Eur. Rev. Med. Pharmacol. Sci. 2019, 23, 1751–1761. [Google Scholar] [CrossRef]
  50. Wang, L.; Sun, M.; Cao, Y.; Ma, L.; Shen, Y.; Velikanova, A.A.; Li, X.; Sun, C.; Zhao, Y. miR-34a regulates lipid metabolism by targeting SIRT1 in non-alcoholic fatty liver disease with iron overload. Arch. Biochem. Biophys. 2020, 695, 108642. [Google Scholar] [CrossRef]
  51. Xiao, K.; Luo, X.; Wang, X.; Gao, Z. MicroRNA-185 regulates transforming growth factor-β1 and collagen-1 in hypertrophic scar fibroblasts. Mol. Med. Rep. 2017, 15, 1489–1496. [Google Scholar] [CrossRef][Green Version]
  52. Li, K.P.; Fang, Y.P.; Liao, J.Q.; Duan, J.D.; Feng, L.G.; Luo, X.Z.; Liang, Z.J. Upregulation of miR-598 promotes cell proliferation and cell cycle progression in human colorectal carcinoma by suppressing INPP5E expression. Mol. Med. Rep. 2018, 17, 2991–2997. [Google Scholar] [CrossRef][Green Version]
  53. Xiao, Y. MiR-486-5p inhibits the hyperproliferation and production of collagen in hypertrophic scar fibroblasts via IGF1/PI3K/AKT pathway. J. Dermatolog. Treat. 2020, 32, 973–982. [Google Scholar] [CrossRef]
  54. Pedersen, I.M.; Cheng, G.; Wieland, S.; Volinia, S.; Croce, C.M.; Chisari, F.V.; David, M. Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 2007, 449, 919–922. [Google Scholar] [CrossRef] [PubMed]
  55. Feng, H.J.; Ouyang, W.; Liu, J.H.; Sun, Y.G.; Hu, R.; Huang, L.H.; Xian, J.L.; Jing, C.F.; Zhou, M.J. Global microRNA profiles and signaling pathways in the development of cardiac hypertrophy. Braz. J. Med. Biol. Res. 2014, 47, 361–368. [Google Scholar] [CrossRef] [PubMed][Green Version]
  56. Chaudhari, U.; Nemade, H.; Gaspar, J.A.; Hescheler, J.; Hengstler, J.G.; Sachinidis, A. MicroRNAs as early toxicity signatures of doxorubicin in human-induced pluripotent stem cell-derived cardiomyocytes. Arch. Toxicol. 2016, 90, 3087–3098. [Google Scholar] [CrossRef][Green Version]
  57. Xia, X.; Wang, S.; Ni, B.; Xing, S.; Cao, H.; Zhang, Z.; Yu, F.; Zhao, E.; Zhao, G. Hypoxic gastric cancer-derived exosomes promote progression and metastasis via MiR-301a-3p/PHD3/HIF-1α positive feedback loop. Oncogene 2020, 39, 6231–6244. [Google Scholar] [CrossRef]
  58. Zhang, L.; Li, J.; Cui, L.; Shang, J.; Tian, F.; Wang, R.; Xing, G. Retraction notice to MicroRNA-30b promotes lipopolysaccharide-induced in fl ammatory injury and alleviates autophagy through JNK and NF- κ B. Biomed. Pharmacother. 2020, 128, 266021. [Google Scholar]
  59. Guan, C.; Wang, Y. LncRNA CASC9 attenuates lactate dehydrogenase-mediated oxidative stress and inflammation in spinal cord injury via sponging miR-383-5p. Inflammation 2021, 44, 923–933. [Google Scholar] [CrossRef]
  60. Sun, R.; Ge, L.; Cao, Y.; Wu, W.; Wu, Y.; Zhu, H.; Li, J.; Yu, D. Corrigendum to “MiR-429 regulates blood-spinal cord barrier permeability by targeting Krüppel-like factor 6”. Biochem. Biophys. Res. Commun. 2020, 525, 740–746. [Google Scholar] [CrossRef]
  61. Chen, X.F.; Zhang, L.J.; Zhang, J.; Dou, X.; Shao, Y.; Jia, X.J.; Zhang, W.; Yu, B. MiR-151a is involved in the pathogenesis of atopic dermatitis by regulating interleukin-12 receptor β2. Exp. Dermatol. 2018, 27, 427–432. [Google Scholar] [CrossRef]
  62. Xiao, S.; Zhang, M.; Liu, C.; Wang, D. MiR-514 attenuates proliferation and increases chemoresistance by targeting ATP binding cassette subfamily in ovarian cancer. Mol. Genet. Genom. 2018, 293, 1159–1167. [Google Scholar] [CrossRef]
  63. Chu, H.T.; Li, L.; Jia, M.; Diao, L.L.; Li, Z.B. Correlation between serum microRNA-136 levels and RAAS biochemical markers in patients with essential hypertension. Eur. Rev. Med. Pharmacol. Sci. 2020, 24, 11761–11767. [Google Scholar] [CrossRef]
  64. Mishima, Y.; Stahlhut, C.; Giraldez, A.J. miR-1-2 Gets to the Heart of the Matter. Cell 2007, 20, 247–249. [Google Scholar] [CrossRef] [PubMed][Green Version]
  65. Qi, B.; Dong, Y.; Qiao, X.L. Effects of miR-18a on proliferation and apoptosis of gastric cancer cells by regulating RUNX1. Eur. Rev. Med. Pharmacol. Sci. 2020, 24, 9957–9964. [Google Scholar] [CrossRef] [PubMed]
  66. Jin, H.; Yu, M.; Lin, Y.; Hou, B.; Wu, Z.; Li, Z.; Sun, J. MiR-502-3P suppresses cell proliferation, migration, and invasion in hepatocellular carcinoma by targeting SET. Onco. Targets. Ther. 2016, 9, 3281–3289. [Google Scholar] [CrossRef] [PubMed]
  67. Zhang, Y.; Chu, X.; Wei, Q. Mir-451 promotes cell apoptosis and inhibits autophagy in pediatric acute myeloid leukemia by targeting hmgb1. J. Environ. Pathol. Toxicol. Oncol. 2021, 40, 45–53. [Google Scholar] [CrossRef]
  68. Rodosthenous, R.S.; Coull, B.A.; Lu, Q.; Vokonas, P.S.; Schwartz, J.D.; Baccarelli, A.A. Ambient particulate matter and microRNAs in extracellular vesicles: A pilot study of older individuals. Part. Fibre Toxicol. 2016, 13, 13. [Google Scholar] [CrossRef][Green Version]
  69. Wang, Z.; Liu, W.; Wang, C.; Ai, Z. Mir-873-5p inhibits cell migration and invasion of papillary thyroid cancer via regulation of CXCL16. Onco. Targets. Ther. 2020, 13, 1037–1046. [Google Scholar] [CrossRef][Green Version]
  70. Tu, H.; Wei, G.; Cai, Q.; Chen, X.X.; Sun, Z.; Cheng, C.; Zhang, L.; Feng, Y.; Zhou, H.; Zhou, B.; et al. MicroRNA-212 inhibits hepatocellular carcinoma cell proliferation and induces apoptosis by targeting FOXAI. Onco. Targets. Ther. 2015, 24, 2227–2235. [Google Scholar] [CrossRef][Green Version]
  71. Zhang, X.; Zhang, Y.; Dou, L. MiR-552 promotes the proliferation and metastasis of cervical cancer cells through targeting MUC15 pathway. J. Cancer 2021, 12, 6094–6104. [Google Scholar] [CrossRef]
  72. Fang, L.; Xu, X.; Lu, Y.; Wu, Y.Y.; Li, J.J. MicroRNA-495 attenuates proliferation and inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes through attenuating β-catenin pathway. J. Biol. Regul. Homeost. Agents 2020, 34, 837–844. [Google Scholar] [CrossRef]
  73. Zhang, K.; Guo, L. MiR-767 promoted cell proliferation in human melanoma by suppressing CYLD expression. Gene 2018, 641, 272–278. [Google Scholar] [CrossRef]
  74. Sun, L.; Trajkovski, M. MiR-27 orchestrates the transcriptional regulation of brown adipogenesis. Metabolism 2014, 63, 272–282. [Google Scholar] [CrossRef] [PubMed]
  75. Si, Z.; Yu, L.; Jing, H.; Wu, L.; Wang, X. Oncogenic lncRNA ZNF561-AS1 is essential for colorectal cancer proliferation and survival through regulation of miR-26a-3p/miR-128-5p-SRSF6 axis. J. Exp. Clin. Cancer Res. 2021, 40, 78. [Google Scholar] [CrossRef] [PubMed]
  76. Tao, X.; Yang, X.; Wu, K.; Yang, L.; Huang, Y.; Jin, Q.; Chen, S. miR-629–5p promotes growth and metastasis of hepatocellular carcinoma by activating β-catenin. Exp. Cell Res. 2019, 15, 124–130. [Google Scholar] [CrossRef] [PubMed]
  77. Liu, X.; Gan, L.; Zhang, J. miR-543 inhibites cervical cancer growth and metastasis by targeting TRPM7. Chem. Biol. Interact. 2019, 302, 83–92. [Google Scholar] [CrossRef]
  78. Zhang, M.; Muralimanoharan, S.; Wortman, A.C.; Mendelson, C.R. Primate-specific miR-515 family members inhibit key genes in human trophoblast differentiation and are upregulated in preeclampsia. Proc. Natl. Acad. Sci. USA 2016, 113, 7069–7076. [Google Scholar] [CrossRef][Green Version]
  79. Witwer, K.W.; Sarbanes, S.L.; Liu, J.; Clements, J.E. A plasma microRNA signature of acute lentiviral infection: Biomarkers of central nervous system disease. AIDS 2011, 25, 2057–2067. [Google Scholar] [CrossRef][Green Version]
  80. Li, B.; Wang, Y.; Li, S.; He, H.; Sun, F.; Wang, C.; Lu, Y.; Wang, X.; Tao, B. Decreased expression of miR-378 correlates with tumor invasiveness and poor prognosis of patients with glioma. Int. J. Clin. Exp. Pathol. 2015, 8, 7016–7021. [Google Scholar]
  81. Li, Q.; Tian, Y.; Liang, Y.; Li, C. CircHIPK3/miR-876-5p/PIK3R1 axis regulates regulation proliferation, migration, invasion, and glutaminolysis in gastric cancer cells. Cancer Cell Int. 2020, 13, 391. [Google Scholar] [CrossRef]
  82. Guo, M.; Jiang, Z.; Zhang, X.; Lu, D.; Ha, A.D.; Sun, J.; Du, W.; Wu, Z.; Hu, L.; Khadarian, K.; et al. miR-656 inhibits glioma tumorigenesis through repression of BMPR1A. Carcinogenesis 2014, 35, 1698–1706. [Google Scholar] [CrossRef][Green Version]
  83. Lv, L.; Wang, X.; Ma, T. MicroRNA-944 inhibits the malignancy of hepatocellular carcinoma by directly targeting IGF-1R and deactivating the PI3K/Akt signaling pathway. Cancer Manag. Res. 2019, 11, 2531–2543. [Google Scholar] [CrossRef][Green Version]
  84. Zhang, W.; Zhong, B.; Zhang, C.; Luo, C.; Zhan, Y. miR-373 regulates inflammatory cytokine-mediated chondrocyte proliferation in osteoarthritis by targeting the P2X7 receptor. FEBS Open Bio 2018, 8, 325–331. [Google Scholar] [CrossRef] [PubMed][Green Version]
  85. Aqeilan, R.I.; Calin, G.A.; Croce, C.M. MiR-15a and miR-16-1 in cancer: Discovery, function and future perspectives. Cell Death Differ. 2010, 17, 215–220. [Google Scholar] [CrossRef] [PubMed][Green Version]
  86. Yang, Z.; Wei, Z.; Wu, X.; Yang, H. Screening of exosomal miRNAs derived from subcutaneous and visceral adipose tissues: Determination of targets for the treatment of obesity and associated metabolic disorders. Mol. Med. Rep. 2018, 18, 3314–3324. [Google Scholar] [CrossRef] [PubMed][Green Version]
  87. Xu, Y.; Wang, L.; Jiang, L.; Zhang, X. Novel MicroRNA Biomarkers, miR-142-5p, miR-550a, miR-1826, and miR-1201, Were Identified for Primary Melanoma. J. Comput. Biol. 2020, 27, 815–824. [Google Scholar] [CrossRef]
  88. Jiang, X.; Huang, H.; Li, Z.; He, C.; Li, Y.; Chen, P.; Gurbuxani, S.; Arnovitz, S.; Hong, G.M.; Price, C.; et al. miR-495 is a tumor-suppressor microRNA down-regulated in MLL-rearranged leukemia. Proc. Natl. Acad. Sci. USA 2012, 109, 19397–19402. [Google Scholar] [CrossRef][Green Version]
  89. Wei, Q.; Tu, Y.; Zuo, L.; Zhao, J.; Chang, Z.; Zou, Y.; Qiu, J. MiR-345-3p attenuates apoptosis and inflammation caused by oxidized low-density lipoprotein by targeting TRAF6 via TAK1/p38/NF-kB signaling in endothelial cells. Life Sci. 2020, 241, 117142. [Google Scholar] [CrossRef]
  90. Xu, X.; Zheng, S. MiR-887-3p negatively regulates StARD13 and promotes pancreatic cancer progression. Cancer Manag. Res. 2020, 12, 6137–6147. [Google Scholar] [CrossRef]
  91. Wu, K.; Yu, Z.; Tang, Z.; Wei, W.; Xie, D.; Xie, Y.; Xiao, Q. MiR-877-5p suppresses gastric cancer cell proliferation through targeting FOXM1. Onco. Targets. Ther. 2020, 13, 4731–4742. [Google Scholar] [CrossRef]
  92. Muti, P.; Donzelli, S.; Sacconi, A.; Hossain, A.; Ganci, F.; Frixa, T.; Sieri, S.; Krogh, V.; Berrino, F.; Biagioni, F.; et al. MiRNA-513a-5p inhibits progesterone receptor expression and constitutes a risk factor for breast cancer: The hOrmone and Diet in the ETiology of breast cancer prospective study. Carcinogenesis 2018, 39, 98–108. [Google Scholar] [CrossRef][Green Version]
  93. Zhu, F.; Li, H.; Ding, F.; Guo, H.; Mou, H.; Ma, J. MiR-422a in gastric cancer cells directly targets CDC40 and modulates cell proliferation. Am. J. Transl. Res. 2020, 12, 4693. [Google Scholar]
  94. Wang, Y.; Yang, L.; Chen, T.; Liu, X.; Guo, Y.; Zhu, Q.; Tong, X.; Yang, W.; Xu, Q.; Huang, D.; et al. A novel lncRNA MCM3AP-AS1 promotes the growth of hepatocellular carcinoma by targeting miR-194-5p/FOXA1 axis. Mol. Cancer 2019, 18, 28. [Google Scholar] [CrossRef] [PubMed]
  95. Zhang, T.; Hu, J.; Wang, X.; Zhao, X.; Li, Z.; Niu, J.; Steer, C.J.; Zheng, G.; Song, G. MicroRNA-378 promotes hepatic inflammation and fibrosis via modulation of the NF-κB-TNFα pathway. J. Hepatol. 2019, 70, 87–96. [Google Scholar] [CrossRef] [PubMed]
  96. Zhao, J.P.; Chen, L.L. Circular rna mat2b induces colorectal cancer proliferation via sponging mir-610, resulting in an increased e2f1 expression. Cancer Manag. Res. 2020, 12, 7107. [Google Scholar] [CrossRef] [PubMed]
  97. Wang, F.; Long, G.; Zhao, C.; Li, H.; Chaugai, S.; Wang, Y.; Chen, C.; Wang, D.W. Atherosclerosis-related circulating miRNAs as novel and sensitive predictors for acute myocardial infarction. PLoS ONE 2014, 9, e105734. [Google Scholar] [CrossRef][Green Version]
  98. Chen, Z.; Li, Y.; Tan, B.; Li, F.; Zhao, Q.; Fan, L.; Zhang, Z.; Zhao, X.; Liu, Y.; Wang, D. Long Non-coding RNA ASNR Targeting miR-519e-5p Promotes Gastric Cancer Development by Regulating FGFR2. Front. Cell Dev. Biol. 2021, 9, 679176. [Google Scholar] [CrossRef]
  99. Chen, F.; Liu, M.; Yu, Y.; Sun, Y.; Li, J.; Hu, W.; Wang, X.; Tong, D. LINC00958 regulated miR-627-5p/YBX2 axis to facilitate cell proliferation and migration in oral squamous cell carcinoma. Cancer Biol. Ther. 2019, 20, 1270–1280. [Google Scholar] [CrossRef]
  100. Liang, T.; Guo, L.; Liu, C. Genome-wide analysis of mir-548 gene family reveals evolutionary and functional implications. J. Biomed. Biotechnol. 2012, 2012, 679563. [Google Scholar] [CrossRef][Green Version]
  101. Wang, L.; Li, H. MiR-770-5p facilitates podocyte apoptosis and inflammation in diabetic nephropathy by targeting TIMP3. Biosci. Rep. 2020, 40, BSR20193653. [Google Scholar] [CrossRef][Green Version]
  102. Li, J.; Wang, L.; He, F.; Li, B.; Han, R. Long noncoding RNA LINC00629 restrains the progression of gastric cancer by upregulating AQP4 through competitively binding to miR-196b-5p. J. Cell. Physiol. 2020, 235, 2973–2985. [Google Scholar] [CrossRef]
  103. Zhu, H.; Hu, Y.; Wang, C.; Zhang, X.; He, D. CircGCN1L1 promotes synoviocyte proliferation and chondrocyte apoptosis by targeting miR-330-3p and TNF-α in TMJ osteoarthritis. Cell Death Dis. 2020, 11, 284. [Google Scholar] [CrossRef]
  104. Liu, T.; Feng, X.; Liao, Y. miR-617 Promotes the Growth of IL-22-Stimulated Keratinocytes Through Regulating FOXO4 Expression. Biochem. Genet. 2021, 59, 547–559. [Google Scholar] [CrossRef] [PubMed]
  105. Chen, S.; Tang, Y.; Liu, Y.; Zhang, P.; Lv, L.; Zhang, X.; Jia, L.; Zhou, Y. Exosomes derived from miR-375-overexpressing human adipose mesenchymal stem cells promote bone regeneration. Cell Prolif. 2019, 52, e12669. [Google Scholar] [CrossRef] [PubMed][Green Version]
  106. Liu, S.; Gong, Y.; Xu, X.D.; Shen, H.; Gao, S.; Bao, H.D.; Guo, S.B.; Yu, X.F.; Gong, J. MicroRNA-936/ERBB4/Akt axis exhibits anticancer properties of gastric cancer through inhibition of cell proliferation, migration, and invasion. Kaohsiung J. Med. Sci. 2021, 37, 111–120. [Google Scholar] [CrossRef]
  107. Wang, P.; Wang, Z.; Liu, G.; Jin, C.; Zhang, Q.; Man, S.; Wang, Z. MiR-657 promotes macrophage polarization toward M1 by targeting FAM46C in gestational diabetes mellitus. Mediat. Inflamm. 2019, 2019, 4851214. [Google Scholar] [CrossRef] [PubMed][Green Version]
  108. Garros, R.F.; Paul, R.; Connolly, M.; Lewis, A.; Garfield, B.E.; Natanek, S.A.; Bloch, S.; Mouly, V.; Griffiths, M.J.; Polkey, M.I.; et al. MicroRNA-542 promotes mitochondrial dysfunction and SMAD activity and is elevated in intensive care unit–acquired weakness. Am. J. Respir. Crit. Care Med. 2017, 196, 1422–1433. [Google Scholar] [CrossRef]
  109. Chen, Y.; Yu, H.; Zhu, D.; Liu, P.; Yin, J.; Liu, D.; Zheng, M.; Gao, J.; Zhang, C.; Gao, Y. miR-136-3p targets PTEN to regulate vascularization and bone formation and ameliorates alcohol-induced osteopenia. FASEB J. 2020, 34, 5348–5362. [Google Scholar] [CrossRef] [PubMed][Green Version]
  110. Xu, Y. MicroRNA-136-3p inhibits glioma tumorigenesis in vitro and in vivo by targeting KLF7. World J. Surg. Oncol. 2020, 18, 1–10. [Google Scholar] [CrossRef]
  111. Xue, Q.; Yang, D.; Zhang, J.; Gan, P.; Lin, C.; Lu, Y.; Zhang, W.; Zhang, L.; Guang, X. USP7, negatively regulated by miR-409-5p, aggravates hypoxia-induced cardiomyocyte injury. APMIS 2021, 129, 152–162. [Google Scholar] [CrossRef]
  112. Wang, Y.; Lin, W.; Ju, J. MicroRNA-409-5p promotes retinal neovascularization in diabetic retinopathy. Cell Cycle 2020, 19, 1314–1325. [Google Scholar] [CrossRef]
  113. Fan, X.D.; Luo, Y.; Wang, J.; An, N. MiR-154-3p and miR-487-3p synergistically modulate RHOA signaling in the carcinogenesis of thyroid cancer. Biosci. Rep. 2020, 40, BSR20193158. [Google Scholar] [CrossRef][Green Version]
  114. Ma, J.; Wu, D.; Yi, J.; Yi, Y.; Zhu, X.; Qiu, H.; Kong, R.; Lin, J.; Qian, J.; Deng, Z. MiR-378 promoted cell proliferation and inhibited apoptosis by enhanced stem cell properties in chronic myeloid leukemia K562 cells. Biomed. Pharmacother. 2019, 112, 108623. [Google Scholar] [CrossRef] [PubMed]
  115. Tang, B.; Xuan, L.; Tang, M.; Wang, H.; Zhou, J.; Liu, J.; Wu, S.; Li, M.; Wang, X.; Zhang, H. miR-93-3p alleviates lipopolysaccharide-induced inflammation and apoptosis in H9c2 cardiomyocytes by inhibiting toll-like receptor 4. Pathol. Res. Pract. 2018, 214, 1686–1693. [Google Scholar] [CrossRef] [PubMed]
  116. Jin, W.; Chen, L.; Gao, F.; Yang, M.; Liu, Y.; Wang, B. Down-regulation of miR-556-3p inhibits hemangioma cell proliferation and promotes apoptosis by targeting VEGFC. Cell. Mol. Biol. 2020, 66, 204–207. [Google Scholar] [CrossRef] [PubMed]
  117. Yang, X.; Yang, S.; Song, J.; Yang, W.; Ji, Y.; Zhang, F.; Rao, J. Dysregulation of miR-23b-5p promotes cell proliferation via targeting FOXM1 in hepatocellular carcinoma. Cell Death Discov. 2021, 7, 1–12. [Google Scholar] [CrossRef] [PubMed]
  118. Zhou, R.; Mao, Y.; Xiong, L.; Li, L. Integrated Transcriptome Analysis of microRNA and mRNA in Mouse Skin Derived Precursors (SKPs) and SKP Derived Fibroblast (SFBs) by RNA-Seq. Curr. Genomics 2018, 20, 49–60. [Google Scholar] [CrossRef] [PubMed]
  119. Tang, P. Clinical diagnostic value of circulating serum miR-509-3p in pulmonary arterial hypertension with congenital heart disease. Hell. J. Cardiol. 2020, 61, 26–30. [Google Scholar] [CrossRef]
  120. Stark, M.S.; Bonazzi, V.F.; Boyle, G.M.; Palmer, J.M.; Symmons, J.; Lanagan, C.M.; Schmidt, C.W.; Herington, A.C.; Ballotti, R.; Pollock, P.M.; et al. miR-514a regulates the tumour suppressor NF1 and modulates BRAFi sensitivity in melanoma. Oncotarget 2015, 6, 17753. [Google Scholar] [CrossRef][Green Version]
  121. Wang, Y.; Zhang, K.; Yuan, X.; Xu, N.; Zhao, S.; Hou, L.; Yang, L.; Zhang, N. MiR-431-5p regulates cell proliferation and apoptosis in fibroblast-like synoviocytes in rheumatoid arthritis by targeting XIAP. Arthritis Res. Ther. 2020, 22, 231. [Google Scholar] [CrossRef]
  122. Wang, Y.; Lei, X.; Gao, C.; Xue, Y.; Li, X.; Wang, H.; Feng, Y. MiR-506-3p suppresses the proliferation of ovarian cancer cells by negatively regulating the expression of MTMR6. J. Biosci. 2019, 44, 126. [Google Scholar] [CrossRef]
  123. Zhu, B.; Tian, T.; Zhao, M. MiR-645 promotes proliferation and migration of non-small cell lung cancer cells by targeting TP53I11. Eur. Rev. Med. Pharmacol. Sci. 2020, 24, 6150–6156. [Google Scholar] [CrossRef]
  124. Zhang, Y.; Wang, Y.; Wei, Y.; Li, M.; Yu, S.; Ye, M.; Zhang, H.; Chen, S.; Liu, W.; Zhang, J. MiR-129-3p promotes docetaxel resistance of breast cancer cells via CP110 inhibition. Sci. Rep. 2015, 5, 15424. [Google Scholar] [CrossRef] [PubMed]
  125. Huang, Y.; Jiang, L.; Wei, G. Circ_0006168 promotes the migration, invasion and proliferation of esophageal squamous cell carcinoma cells via mir-516b-5p-dependent regulation of xbp1. Onco. Targets. Ther. 2021, 14, 475–2488. [Google Scholar] [CrossRef] [PubMed]
  126. Kong, M.; Han, Y.; Zhao, Y.; Zhang, H. miR-512-3p Overcomes Resistance to Cisplatin in Retinoblastoma by Promoting Apoptosis Induced by Endoplasmic Reticulum Stress. Med. Sci. Monit. 2020, 26, 923817. [Google Scholar] [CrossRef] [PubMed]
  127. Wang, H.; Guo, Y.; Mi, N.; Zhou, L. miR-101-3p and miR-199b-5p promote cell apoptosis in oral cancer by targeting BICC1. Mol. Cell. Probes 2020, 52, 101567. [Google Scholar] [CrossRef]
  128. Liao, Z.J.; Zheng, Q.; Wei, T.; Zhang, Y.B.; Ma, J.Q.; Zhao, Z.; Sun, H.F.; Nan, K.J. MicroRNA-561 Affects Proliferation and Cell Cycle Transition through PTEN/AKT Signaling Pathway by Targeting P-REX2a in NSCLC. Oncol. Res. 2020, 28, 147–159. [Google Scholar] [CrossRef]
  129. He, Q.; Liu, N.; Hu, F.; Shi, Q.; Pi, X.; Chen, H.; Li, J.; Zhang, B. Circ_0061012 contributes to IL-22-induced proliferation, migration and invasion in keratinocytes through miR-194-5p/GAB1 axis in psoriasis. Biosci. Rep. 2021, 4, BSR20203130. [Google Scholar] [CrossRef]
  130. Wang, Y.P.; Li, H.Q.; Chen, J.X.; Kong, F.G.; Mo, Z.H.; Wang, J.Z.; Huang, K.M.; Li, X.N.; Yan, Y. Overexpression of XIST facilitates cell proliferation, invasion and suppresses cell apoptosis by reducing radio-sensitivity of glioma cells via miR-329-3p/CREB1 axis. Eur. Rev. Med. Pharmacol. Sci. 2020, 24, 3190–3203. [Google Scholar] [CrossRef]
  131. Wang, Y.F.; Lian, X.L.; Zhong, J.Y.; Su, S.X.; Xu, Y.F.; Xie, X.F.; Wang, Z.P.; Li, W.; Zhang, L.; Che, D.; et al. Serum exosomal microRNA let-7i-3p as candidate diagnostic biomarker for Kawasaki disease patients with coronary artery aneurysm. IUBMB Life 2019, 71, 891–900. [Google Scholar] [CrossRef]
  132. Liu, Z.; Dou, C.; Yao, B.; Xu, M.; Ding, L.; Wang, Y.; Jia, Y.; Li, Q.; Zhang, H.; Tu, K.; et al. Methylation-mediated repression of microRNA-129-2 suppresses cell aggressiveness by inhibiting high mobility group box 1 in human hepatocellular carcinoma. Oncotarget 2016, 7, 36909–36923. [Google Scholar] [CrossRef][Green Version]
  133. Zhao, G.; Wang, T.; Huang, Q.K.; Pu, M.; Sun, W.; Zhang, Z.C.; Ling, R.; Tao, K.S. MicroRNA-548a-5p promotes proliferation and inhibits apoptosis in hepatocellular carcinoma cells by targeting Tg737. World J. Gastroenterol. 2016, 22, 5364–5373. [Google Scholar] [CrossRef]
  134. Jiang, Y.; Wang, N.; Yin, D.; Li, Y.K.; Guo, L.; Shi, L.P.; Huang, X. Changes in the Expression of Serum MiR-887-5p in Patients with Endometrial Cancer. Int. J. Gynecol. Cancer 2016, 26, 1143–1147. [Google Scholar] [CrossRef] [PubMed]
  135. Moura, S.R.; Bras, J.P.; Freitas, J.; Osório, H.; Barbosa, M.A.; Santos, S.G.; Almeida, M.I. miR-99a in bone homeostasis: Regulating osteogenic lineage commitment and osteoclast differentiation. Bone 2020, 134, 115303. [Google Scholar] [CrossRef] [PubMed]
  136. Fan, Y.; Hao, J.; Cen, X.; Song, K.; Yang, C.; Xiao, S.; Cheng, S. Downregulation of miR-487a-3p suppresses the progression of non-small cell lung cancer via targeting Smad7. Drug Dev. Res. 2021. [Google Scholar] [CrossRef]
  137. Liu, W.; Yang, Y.J.; An, Q. LINC00963 promotes ovarian cancer proliferation, migration and EMT via the miR-378g/CHI3L1 axis. Cancer Manag. Res. 2020, 12, 463–473. [Google Scholar] [CrossRef] [PubMed][Green Version]
  138. Li, F.; Liu, H.; Cheng, Y.; Yang, J.; Liu, Y.; Wang, Y.; Yang, Z.; Shi, C.; Xu, Y. Association of variants in microRNA with Parkinson’s disease in Chinese Han population. Neurol. Sci. 2018, 39, 353–357. [Google Scholar] [CrossRef]
  139. Dong, L.; Zheng, Y.; Gao, L.; Luo, X. lncRNA NEAT1 prompts autophagy and apoptosis in MPTP-induced Parkinson’s disease by impairing miR-374c-5p. Acta Biochim. Biophys. Sin. 2021, 53, 870–882. [Google Scholar] [CrossRef]
  140. Zhu, M.; Zhang, N.; He, S.; Yan, R.; Zhang, J. MicroRNA-106a functions as an oncogene in human gastric cancer and contributes to proliferation and metastasis in vitro and in vivo. Clin. Exp. Metastasis 2016, 3, 509–519. [Google Scholar] [CrossRef]
  141. Long, C.Y.; Xiao, Y.X.; Li, S.Y.; Tang, X.B.; Yuan, Z.W.; Bai, Y.Z. Upregulation of miR-92a-2-5p potentially contribute to anorectal malformations by inhibiting proliferation and enhancing apoptosis via PRKCA/β-catenin. Biomed. Pharmacother. 2020, 127, 110117. [Google Scholar] [CrossRef]
  142. Zhu, L.M.; Li, N. Downregulation of long noncoding RNA TUSC7 promoted cell growth, invasion and migration through sponging with miR-616-5p/GSK3β pathway in ovarian cancer. Eur. Rev. Med. Pharmacol. Sci. 2020, 24, 7253–7265. [Google Scholar] [CrossRef]
  143. Fu, L.; Li, Z.; Zhu, J.; Wang, P.; Fan, G.; Dai, Y.; Zheng, Z.; Liu, Y. Serum expression levels of microRNA-382-3p, -598-3p, -1246 and -184 in breast cancer patients. Oncol. Lett. 2016, 12, 269–274. [Google Scholar] [CrossRef][Green Version]
  144. Li, G.; Xu, Y.; Wang, S.; Yan, W.; Zhao, Q.; Guo, J. MiR-873-5p inhibits cell migration, invasion and epithelial-mesenchymal transition in colorectal cancer via targeting ZEB1. Pathol. Res. Pract. 2019, 215, 34–39. [Google Scholar] [CrossRef] [PubMed]
  145. Liu, Z.; Su, D.; Qi, X.; Ma, J. MiR-500a-5p promotes glioblastoma cell proliferation, migration and invasion by targeting chromodomain helicase DNA binding protein 5. Mol. Med. Rep. 2018, 18, 2689–2696. [Google Scholar] [CrossRef] [PubMed]
  146. Liu, Z.; He, C.; Qu, Y.; Chen, X.; Zhu, H.; Xiang, B. MiR-659-3p regulates the progression of chronic myeloid leukemia by targeting SPHK1. Int. J. Clin. Exp. Pathol. 2018, 11, 2470. [Google Scholar]
  147. Lin, Q.; Jia, Y.; Zhang, D.; Jin, H. NCK1-AS1 promotes the progression of melanoma by accelerating cell proliferation and migration via targeting miR-526b-5p/ADAM15 axis. Cancer Cell Int. 2021, 21, 1–10. [Google Scholar] [CrossRef]
  148. Zhu, F.; Li, Q.; Li, J.; Li, B.; Li, D. Long noncoding Mirt2 reduces apoptosis to alleviate myocardial infarction through regulation of the miR-764/PDK1 axis. Lab. Investig. 2021, 101, 165–176. [Google Scholar] [CrossRef] [PubMed]
  149. Zhao, S.; Mi, Y.; Guan, B.; Zheng, B.; Wei, P.; Gu, Y.; Zhang, Z.; Cai, S.; Xu, Y.; Li, X.; et al. Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer. J. Hematol. Oncol. 2020, 13, 156. [Google Scholar] [CrossRef]
  150. Ye, X.Y.; Xu, L.; Lu, S.; Chen, Z.W. Mir-516a-5p inhibits the proliferation of non-small cell lung cancer by targeting hist3h2a. Int. J. Immunopathol. Pharmacol. 2019, 33, 2058738419841481. [Google Scholar] [CrossRef] [PubMed]
  151. Yuan, X.; Ma, R.; Yang, S.; Jiang, L.; Wang, Z.; Zhu, Z.; Li, H. miR-520g and miR-520h overcome bortezomib resistance in multiple myeloma via suppressing APE1. Cell Cycle 2019, 18, 1660–1669. [Google Scholar] [CrossRef]
  152. Wang, J.; Wang, H.; Liu, A.; Fang, C.; Hao, J.; Wang, Z. Lactate dehydrogenase A negatively regulated by miRNAs promotes aerobic glycolysis and is increased in colorectal cancer. Oncotarget 2015, 6, 19465. [Google Scholar] [CrossRef]
  153. Su, X.; Gao, C.; Feng, X.; Jiang, M. miR-613 suppresses migration and invasion in esophageal squamous cell carcinoma via the targeting of G6PD. Exp. Ther. Med. 2020, 19, 3081–3089. [Google Scholar] [CrossRef][Green Version]
  154. Wang, M.; Zhao, H.Y.; Zhang, J.L.; Wan, D.M.; Li, Y.M.; Jiang, Z.X. Dysregulation of LncRNA ANRIL mediated by miR-411–3p inhibits the malignant proliferation and tumor stem cell like property of multiple myeloma via hypoxia-inducible factor 1α. Exp. Cell Res. 2020, 396, 112280. [Google Scholar] [CrossRef] [PubMed]
  155. Hou, J.; Li, A.L.; Xiong, W.Q.; Chen, R. Hsa Circ 001839 Promoted Inflammation in Renal Ischemia-Reperfusion Injury through NLRP3 by miR-432-3p. Nephron 2021, 145, 540–552. [Google Scholar] [CrossRef] [PubMed]
  156. Fan, R.F.; Cao, C.Y.; Chen, M.H.; Shi, Q.X.; Xu, S.W. Gga-let-7f-3p promotes apoptosis in selenium deficiency-induced skeletal muscle by targeting selenoprotein K. Metallomics 2018, 10, 941–952. [Google Scholar] [CrossRef] [PubMed]
  157. Zhang, B. Guizhi Fuling pills inhibit the proliferation, migration and invasion of human cutaneous malignant melanoma cells by regulating the molecular axis of LncRNA TPT1-AS1/miR-671-5p. Cell. Mol. Biol. 2020, 66, 148–154. [Google Scholar] [CrossRef]
  158. Li, Y.; Kuscu, C.; Banach, A.; Zhang, Q.; Pulkoski-Gross, A.; Kim, D.; Liu, J.; Roth, E.; Li, E.; Shroyer, K.R.; et al. miR-181a-5p inhibits cancer cell migration and angiogenesis via downregulation of matrix metalloproteinase-14. Cancer Res. 2015, 75, 2674–2685. [Google Scholar] [CrossRef] [PubMed][Green Version]
  159. Baker, M.A.; Wang, F.; Liu, Y.; Kriegel, A.J.; Geurts, A.M.; Usa, K.; Xue, H.; Wang, D.; Kong, Y.; Liang, M. MiR-192-5p in the Kidney Protects Against the Development of Hypertension. Hypertension 2019, 73, 399–406. [Google Scholar] [CrossRef]
  160. Zhang, H.; Zhang, Z.; Gao, L.; Qiao, Z.; Yu, M.; Yu, B.; Yang, T. miR-1-3p suppresses proliferation of hepatocellular carcinoma through targeting SOX9. Onco. Targets. Ther. 2019, 12, 2149–2157. [Google Scholar] [CrossRef][Green Version]
  161. Wang, Y.; Zhang, Q. Long Noncoding RNA MALAT1 Knockdown Inhibits Proliferation, Migration, and Invasion and Promotes Apoptosis in Non-Small-Cell Lung Cancer Cells Through Regulating miR-515-3p/TRIM65 Axis. Cancer Biother. Radiopharm. 2020. [Google Scholar] [CrossRef]
  162. Liu, L.; Zhang, H.; Mao, H.; Li, X.; Hu, Y. Exosomal miR-320d derived from adipose tissue-derived MSCs inhibits apoptosis in cardiomyocytes with atrial fibrillation (AF). Artif. Cells Nanomed. Biotechnol. 2019, 47, 3976–3984. [Google Scholar] [CrossRef]
  163. Peng, X.; Wu, M.; Liu, W.; Guo, C.; Zhan, L.; Zhan, X. MiR-502-5p inhibits the proliferation, migration and invasion of gastric cancer cells by targeting SP1. Oncol. Lett. 2020, 20, 2757–2762. [Google Scholar] [CrossRef]
  164. Wu, X.; Chen, B.; Shi, H.; Zhou, J.; Zhou, F.; Cao, J.; Sun, X. miR-758-3p suppresses human bladder cancer cell proliferation, migration and invasion by targeting NOTCH2. Exp. Ther. Med. 2019, 17, 4273–4278. [Google Scholar] [CrossRef]
  165. Pourhanifeh, M.H.; Mahjoubin-Tehran, M.; Karimzadeh, M.R.; Mirzaei, H.R.; Razavi, Z.S.; Sahebkar, A.; Hosseini, N.; Mirzaei, H.; Hamblin, M.R. Autophagy in cancers including brain tumors: Role of MicroRNAs. Cell Commun. Signal. 2020, 18, 88. [Google Scholar] [CrossRef] [PubMed]
  166. Xu, J.; Lei, S.; Sun, S.; Zhang, W.; Zhu, F.; Yang, H.; Xu, Q.; Zhang, B.; Li, H.; Zhu, M.; et al. Mir-324-3p regulates fibroblast proliferation via targeting tgf-β1 in atrial fibrillation. Int. Heart J. 2020, 61, 20–423. [Google Scholar] [CrossRef] [PubMed]
  167. Kordaß, T.; Weber, C.E.M.; Eisel, D.; Pane, A.A.; Osen, W.; Eichmüller, S.B. miR-193b and miR-30c-1* inhibit, whereas miR-576-5p enhances melanoma cell invasion in vitro. Oncotarget 2018, 9, 32507–32522. [Google Scholar] [CrossRef] [PubMed][Green Version]
  168. Li, J.; Shao, W.; Zhao, J. MiR-520a-3p inhibits malignant progression of epithelial ovarian cancer by targeting SUV39H1 expression. Hum. Cell 2021, 34, 570–578. [Google Scholar] [CrossRef]
  169. Fang, Y.; Gu, X.; Li, Z.; Xiang, J.; Chen, Z. miR-449b inhibits the proliferation of SW1116 colon cancer stem cells through downregulation of CCND1 and E2F3 expression. Oncol. Rep. 2013, 30, 399–506. [Google Scholar] [CrossRef] [PubMed]
  170. Díaz-Martínez, M.; Benito-Jardon, L.; Alonso, L.; Koetz-Ploch, L.; Hernando, E.; Teixido, J. miR-204-5p and miR-211-5p contribute to BRAF inhibitor resistance in melanoma. Cancer Res. 2018, 78, 1017–1030. [Google Scholar] [CrossRef] [PubMed][Green Version]
  171. Du, L.; Xu, Z.; Wang, X.; Liu, F. Integrated bioinformatics analysis identifies microRNA-376a-3p as a new microRNA biomarker in patient with coronary artery disease. Am. J. Transl. Res. 2020, 12, 633–648. [Google Scholar]
  172. Han, X.; Du, C.; Chen, Y.; Zhong, X.; Wang, F.; Wang, J.; Liu, C.; Li, M.; Chen, S.; Li, B. Overexpression of miR-939-3p predicts poor prognosis and promotes progression in lung cancer. Cancer Biomark. 2019, 25, 335–342. [Google Scholar] [CrossRef]
  173. Xu, M.; Sun, J.; Yu, Y.; Pang, Q.; Lin, X.; Barakat, M.; Lei, R.; Xu, J. TM4SF1 involves in miR-1-3p/miR-214-5p-mediated inhibition of the migration and proliferation in keloid by regulating AKT/ERK signaling. Life Sci. 2020, 254, 117746. [Google Scholar] [CrossRef]
  174. Van Solingen, C.; Oldebeken, S.R.; Salerno, A.G.; Wanschel, A.C.B.A.; Moore, K.J. High-Throughput Screening Identifies MicroRNAs Regulating Human PCSK9 and Hepatic Low-Density Lipoprotein Receptor Expression. Front. Cardiovasc. Med. 2021, 8, 701. [Google Scholar] [CrossRef] [PubMed]
  175. Sassi, Y.; Avramopoulos, P.; Ramanujam, D.; Grüter, L.; Werfel, S.; Giosele, S.; Brunner, A.D.; Esfandyari, D.; Papadopoulou, A.S.; De Strooper, B.; et al. Cardiac myocyte miR-29 promotes pathological remodeling of the heart by activating Wnt signaling. Nat. Commun. 2017, 8, 1614. [Google Scholar] [CrossRef] [PubMed]
  176. Miao, L.J.; Huang, S.F.; Sun, Z.T.; Gao, Z.Y.; Zhang, R.X.; Liu, Y.; Wang, J. MiR-449c targets c-Myc and inhibits NSCLC cell progression. FEBS Lett. 2013, 587, 1359–1365. [Google Scholar] [CrossRef] [PubMed][Green Version]
  177. Deng, Z.H.; Yu, G.S.; Deng, K.L.; Feng, Z.H.; Huang, Q.; Pan, B.; Deng, J.Z. Hsa_circ_0088233 Alleviates Proliferation, Migration, and Invasion of Prostate Cancer by Targeting hsa-miR-185-3p. Front. Cell Dev. Biol. 2020, 8, 528155. [Google Scholar] [CrossRef]
  178. Ye, W.; Ma, J.; Wang, F.; Wu, T.; He, M.; Li, J.; Pei, R.; Zhang, L.; Wang, Y.; Zhou, J. LncRNA MALAT 1 Regulates miR-144-3p to Facilitate Epithelial-Mesenchymal Transition of Lens Epithelial Cells via the ROS/NRF2/Notch1/Snail Pathway. Oxid. Med. Cell. Longev. 2020, 2020, 8184314. [Google Scholar] [CrossRef]
  179. Watanabe, K.; Yamaji, R.; Ohtsuki, T. MicroRNA-664a-5p promotes neuronal differentiation of SH-SY5Y cells. Genes Cells 2018, 23, 225–233. [Google Scholar] [CrossRef][Green Version]
  180. Huang, D.; Liu, Y.; Gao, L.; Wei, X.; Xu, Y.; Cai, R.; Su, Q. MiR-32-3p Regulates Myocardial Injury Induced by Microembolism and Microvascular Obstruction by Targeting RNF13 to Regulate the Stability of Atherosclerotic Plaques. J. Cardiovasc. Transl. Res. 2021, 1–24. [Google Scholar] [CrossRef]
  181. Wang, G.; Liu, L.; Zhang, J.; Huang, C.; Chen, Y.; Bai, W.; Wang, Y.; Zhao, K.; Li, S. Lncrna hcg11 suppresses cell proliferation and promotes apoptosis via sponging mir-224-3p in non-small-cell lung cancer cells. Onco. Targets. Ther. 2020, 3, 6553–6563. [Google Scholar] [CrossRef]
  182. Pan, X.; He, Y.; Chen, Z.; Yan, G.; Ma, G. Circulating miR-130 is a potential bio signature for early prognosis of acute myocardial infarction. J. Thorac. Dis. 2020, 12, 7320–7325. [Google Scholar] [CrossRef]
  183. Krist, B.; Florczyk, U.; Pietraszek-Gremplewicz, K.; Józkowicz, A.; Dulak, J. The role of miR-378a in metabolism, angiogenesis, and muscle biology. Int. J. Endocrinol. 2015, 2015, 281756. [Google Scholar] [CrossRef][Green Version]
  184. Kurowska, W.; Kuca-Warnawin, E.; Radzikowska, A.; Jakubaszek, M.; Maślińska, M.; Kwiatkowska, B.; Maśliński, W. Monocyte-related biomarkers of rheumatoid arthritis development in undifferentiated arthritis patients—A pilot study. Reumatologia 2018, 56, 10–16. [Google Scholar] [CrossRef] [PubMed][Green Version]
  185. Ma, H.; Huang, C.; Huang, Q.; Li, G.; Li, J.; Huang, B.; Zhong, Q.; Cao, C. Circular RNA circ_0014717 Suppresses Hepatocellular Carcinoma Tumorigenesis Through Regulating miR-668-3p/BTG2 Axis. Front. Oncol. 2021, 10, 3013. [Google Scholar] [CrossRef] [PubMed]
  186. Jiang, M.; Yin, Y.; Xie, L.; He, H. Plasma miR-18 screens acute myocardial infarction from healthy controls by targeting hypoxia inducible factor 1α. Clin. Lab. 2018, 64, 1207–1212. [Google Scholar] [CrossRef]
  187. Lupini, L.; Pepe, F.; Ferracin, M.; Braconi, C.; Callegari, E.; Pagotto, S.; Spizzo, R.; Zagatti, B.; Lanuti, P.; Fornari, F.; et al. Over-expression of the miR-483-3p overcomes the miR-145/TP53 pro-apoptotic loop in hepatocellular carcinoma. Oncotarget 2016, 7, 31361. [Google Scholar] [CrossRef] [PubMed][Green Version]
  188. Pan, Y.; Qin, J.; Sun, H.; Xu, T.; Wang, S.; He, B. MiR-485-5p as a potential biomarker and tumor suppressor in human colorectal cancer. Biomark. Med. 2020, 14, 239–248. [Google Scholar] [CrossRef]
  189. Carlomosti, F.; D’Agostino, M.; Beji, S.; Torcinaro, A.; Rizzi, R.; Zaccagnini, G.; Maimone, B.; Di Stefano, V.; De Santa, F.; Cordisco, S.; et al. Oxidative Stress-Induced miR-200c Disrupts the Regulatory Loop among SIRT1, FOXO1, and eNOS. Antioxid. Redox Signal. 2017, 27, 328–344. [Google Scholar] [CrossRef]
  190. Li, S.N.; Li, P.; Liu, W.H.; Shang, J.J.; Qiu, S.L.; Zhou, M.X.; Liu, H.X. Danhong injection enhances angiogenesis after myocardial infarction by activating MiR-126/ERK/VEGF pathway. Biomed. Pharmacother. 2019, 120, 109538. [Google Scholar] [CrossRef]
  191. Tsai, M.M.; Huang, H.W.; Wang, C.S.; Lee, K.F.; Tsai, C.Y.; Lu, P.H.; Chi, H.C.; Lin, Y.H.; Kuo, L.M.; Lin, K.H. MicroRNA-26b inhibits tumor metastasis by targeting the KPNA2/c-jun pathway in human gastric cancer. Oncotarget 2016, 7, 39511–39526. [Google Scholar] [CrossRef][Green Version]
  192. Skrzypek, K.; Tertil, M.; Golda, S.; Ciesla, M.; Weglarczyk, K.; Collet, G.; Guichard, A.; Kozakowska, M.; Boczkowski, J.; Was, H.; et al. Interplay between heme oxygenase-1 and miR-378 affects non-small cell lung carcinoma growth, vascularization, and metastasis. Antioxid. Redox Signal. 2013, 19, 644–660. [Google Scholar] [CrossRef][Green Version]
  193. Wu, M.; Li, X.; Liu, Q.; Xie, Y.; Yuan, J.; Wanggou, S. miR-526b-3p serves as a prognostic factor and regulates the proliferation, invasion, and migration of glioma through targeting WEEI. Cancer Manag. Res. 2019, 11, 3099–3110. [Google Scholar] [CrossRef][Green Version]
  194. Wang, Y.N.; Xu, F.; Zhang, P.; Wang, P.; Wei, Y.N.; Wu, C.; Cheng, S.J. MicroRNA-575 regulates development of gastric cancer by targeting PTEN. Biomed. Pharmacother. 2019, 113, 108716. [Google Scholar] [CrossRef] [PubMed]
  195. Liang, C.; Xu, Y.; Ge, H.; Xing, B.; Li, G.; Li, G.; Wu, J. MiR-564 inhibits hepatocellular carcinoma cell proliferation and invasion by targeting the GRB2-ERK1/2-AKT axis. Oncotarget 2017, 8, 107543–107557. [Google Scholar] [CrossRef] [PubMed][Green Version]
  196. Li, S.; Xu, Y.N.; Niu, X.; Li, Z.; Wang, J.F. miR-513a-5p targets Bcl-2 to promote dichlorvos induced apoptosis in HK-2 cells. Biomed. Pharmacother. 2018, 108, 876–882. [Google Scholar] [CrossRef] [PubMed]
  197. Shu, W.; Zhang, Y.; Zhang, C.; You, Q.; Zhou, H.; Wen, S. Triclosan inhibits the activation of human periodontal ligament fibroblasts induced by lipopolysaccharide from Porphyromonas gingivalis. J. Biomed. Res. 2021, 35, 206. [Google Scholar] [CrossRef]
  198. Wang, M.; Qiu, R.; Gong, Z.; Zhao, X.; Wang, T.; Zhou, L.; Lu, W.; Shen, B.; Zhu, W.; Xu, W. miR-188-5p emerges as an oncomiRNA to promote gastric cancer cell proliferation and migration via upregulation of SALL4. J. Cell. Biochem. 2019, 120, 15027–15037. [Google Scholar] [CrossRef] [PubMed]
  199. Zhang, X.; Li, M.; Sun, G.; Bai, Y.; Lv, D.; Liu, C. MiR-563 restrains cell proliferation via targeting LIN28B in human lung cancer. Thorac. Cancer 2020, 11, 55–61. [Google Scholar] [CrossRef]
  200. Zhang, W.; Xu, J.; Wang, K.; Tang, X.; He, J. MIR-139-3p suppresses the invasion and migration properties of breast cancer cells by targeting RAB1A. Oncol. Rep. 2019, 42, 1699–1708. [Google Scholar] [CrossRef] [PubMed]
  201. Pan, Y.; Hui, X.; Chong Hoo, R.L.; Ye, D.; Cheung Chan, C.Y.; Feng, T.; Wang, Y.; Ling Lam, K.S.; Xu, A. Adipocyte-secreted exosomal microRNA-34a inhibits M2 macrophage polarization to promote obesity-induced adipose inflammation. J. Clin. Investig. 2019, 129, 834–849. [Google Scholar] [CrossRef][Green Version]
  202. Liu, X.; Feng, J.; Tang, L.; Liao, L.; Xu, Q.; Zhu, S. The regulation and function of mir-21-foxo3a-mir-34b/c signaling in breast cancer. Int. J. Mol. Sci. 2015, 16, 3148–3162. [Google Scholar] [CrossRef][Green Version]
  203. Luo, X.; Zhang, X.; Peng, J.; Chen, Y.; Zhao, W.; Jiang, X.; Su, L.; Xie, M.; Lin, B. miR-371b-5p promotes cell proliferation, migration and invasion in non-small cell lung cancer via SCAI. Biosci. Rep. 2020, 40, BSR290200163. [Google Scholar] [CrossRef]
  204. Zhu, G.; Zhang, W.; Liu, Y.; Wang, S. MiR-371b-5p inhibits endothelial cell apoptosis in monocrotaline-induced pulmonary arterial hypertension via PTEN/PI3K/Akt signaling pathways. Mol. Med. Rep. 2018, 8, 5489–5501. [Google Scholar] [CrossRef] [PubMed][Green Version]
  205. Li, D.; Chen, L.; Zhao, W.; Hao, J.; An, R. MicroRNA-let-7f-1 is induced by lycopene and inhibits cell proliferation and triggers apoptosis in prostate cancer. Mol. Med. Rep. 2016, 13, 2708–2714. [Google Scholar] [CrossRef] [PubMed][Green Version]
  206. Qiu, J.; Hao, Y.; Huang, S.; Ma, Y.; Li, X.; Li, D.; Mao, Y. MIR-557 works as a tumor suppressor in human lung cancers by negatively regulating LEF1 expression. Tumor Biol. 2017, 39, 1010428317709467. [Google Scholar] [CrossRef] [PubMed][Green Version]
  207. Cui, J.; Qi, S.; Liao, R.; Su, D.; Wang, Y.; Xue, S. MiR-574–5p promotes the differentiation of human cardiac fibroblasts via regulating ARID3A. Biochem. Biophys. Res. Commun. 2020, 521, 427–433. [Google Scholar] [CrossRef]
  208. Wang, X.; Shi, J.; Niu, Z.; Wang, J.; Zhang, W. MiR-216a-3p regulates the proliferation, apoptosis, migration, and invasion of lung cancer cells via targeting COPB2. Biosci. Biotechnol. Biochem. 2020, 84, 2014–2027. [Google Scholar] [CrossRef]
  209. Tong, F.; Ying, Y.; Pan, H.; Zhao, W.; Li, H.; Zhan, X. Microrna-466 (Mir-466) functions as a tumor suppressor and prognostic factor in colorectal cancer (CRC). Bosn. J. Basic Med. Sci. 2018, 18, 252–259. [Google Scholar] [CrossRef][Green Version]
  210. He, N.; Liu, L.; Ding, J.; Sun, Y.; Xing, H.; Wang, S. MiR-222-3p ameliorates glucocorticoid-induced inhibition of airway epithelial cell repair through down-regulating GILZ expression. J. Recept. Signal Transduct. 2020, 40, 301–312. [Google Scholar] [CrossRef]
  211. Yang, L.; Liu, Z.M.; Rao, Y.W.; Cui, S.Q.; Wang, H.; Jia, X.J. Downregulation of microRNA-586 Inhibits Proliferation, Invasion and Metastasis and Promotes Apoptosis in Human Osteosarcoma U2-OS Cell Line. Cytogenet. Genome Res. 2015, 146, 268–278. [Google Scholar] [CrossRef]
  212. Ramanathan, S.; Shenoda, B.B.; Lin, Z.; Alexander, G.M.; Huppert, A.; Sacan, A.; Ajit, S.K. Inflammation potentiates miR-939 expression and packaging into small extracellular vesicles. J. Extracell. Vesicles 2019, 8, 1650595. [Google Scholar] [CrossRef][Green Version]
  213. Lin, L.; Wang, Y. MiR-548b-3p regulates proliferation, apoptosis, and mitochondrial function by targeting CIP2A in hepatocellular carcinoma. Biomed Res. Int. 2018, 2018, 7385426. [Google Scholar] [CrossRef][Green Version]
  214. Herrera-Van Oostdam, A.S.; Toro-Ortíz, J.C.; López, J.A.; Noyola, D.E.; García-López, D.A.; Durán-Figueroa, N.V.; Martínez-Martínez, E.; Portales-Pérez, D.P.; Salgado-Bustamante, M.; López-Hernández, Y. Placental exosomes isolated from urine of patients with gestational diabetes exhibit a differential profile expression of microRNAs across gestation. Int. J. Mol. Med. 2020, 46, 546–560. [Google Scholar] [CrossRef] [PubMed]
  215. Mei, L.; Yan, H.; Wang, S.; Guo, C.; Zheng, X.; Yan, B.; Zhao, J.; Yang, A. Upregulation of miR-630 Induced by Oxidative Damage Resists Cell Migration Through Targeting ALCAM in Human Lens Epithelium Cells. Curr. Eye Res. 2020, 45, 153–161. [Google Scholar] [CrossRef] [PubMed]
  216. Yanaka, Y.; Muramatsu, T.; Uetake, H.; Kozaki, K.I.; Inazawa, J. miR-544a induces epithelial-mesenchymal transition through the activation of WNT signaling pathway in gastric cancer. Carcinogenesis 2015, 36, 1363–1371. [Google Scholar] [CrossRef] [PubMed][Green Version]
  217. Lin, Y.X.; Wu, X.B.; Zheng, C.W.; Zhang, Q.L.; Zhang, G.Q.; Chen, K.; Zhan, Q.; An, F.M. Mechanistic Investigation on the Regulation of FABP1 by the IL-6/miR-603 Signaling in the Pathogenesis of Hepatocellular Carcinoma. Biomed Res. Int. 2021, 2021, 8579658. [Google Scholar] [CrossRef]
  218. Cai, W.; Xu, Y.; Yin, J.; Zuo, W.; Su, Z. miR-552-5p facilitates osteosarcoma cell proliferation and metastasis by targeting WIF1. Exp. Ther. Med. 2019, 17, 3781–3788. [Google Scholar] [CrossRef][Green Version]
  219. Chen, Y.; Lei, Y.; Lin, J.; Huang, Y.; Zhang, J.; Chen, K.; Sun, S.; Lin, X. The Linc01260 functions as a tumor suppressor via the miR-562/CYLD/NF-κB pathway in non-small cell lung cancer. Onco. Targets. Ther. 2020, 13, 10707–10719. [Google Scholar] [CrossRef] [PubMed]
  220. Christofides, A.; Papagregoriou, G.; Dweep, H.; Makrides, N.; Gretz, N.; Felekkis, K.; Deltas, C. Evidence for miR-548c-5p regulation of FOXC2 transcription through a distal genomic target site in human podocytes. Cell. Mol. Life Sci. 2020, 77, 2441–2459. [Google Scholar] [CrossRef]
  221. Kijpaisalratana, N.; Nimsamer, P.; Khamwut, A.; Payungporn, S.; Pisitkun, T.; Chutinet, A.; Utoomprurkporn, N.; Kerr, S.J.; Vongvasinkul, P.; Suwanwela, N.C. Serum miRNA125a-5p, miR-125b-5p, and miR-433-5p as biomarkers to differentiate between posterior circulation stroke and peripheral vertigo. BMC Neurol. 2020, 20, 372. [Google Scholar] [CrossRef]
  222. Mao, Q.; Liang, X.L.; Zhang, C.L.; Pang, Y.H.; Lu, Y.X. LncRNA KLF3-AS1 in human mesenchymal stem cell-derived exosomes ameliorates pyroptosis of cardiomyocytes and myocardial infarction through miR-138-5p/Sirt1 axis. Stem Cell Res. Ther. 2019, 10, 393. [Google Scholar] [CrossRef]
  223. Liu, F.; Yu, X.; Huang, H.; Chen, X.; Wang, J.; Zhang, X.; Lin, Q. Upregulation of microRNA-450 inhibits the progression of lung cancer in vitro and in vivo by targeting interferon regulatory factor 2. Int. J. Mol. Med. 2016, 38, 283–290. [Google Scholar] [CrossRef][Green Version]
  224. Luo, Y.; Liu, W.; Tang, P.; Jiang, D.; Gu, C.; Huang, Y.; Gong, F.; Rong, Y.; Qian, D.; Chen, J.; et al. MiR-624-5p promoted tumorigenesis and metastasis by suppressing hippo signaling through targeting PTPRB in osteosarcoma cells. J. Exp. Clin. Cancer Res. 2019, 38, 488. [Google Scholar] [CrossRef] [PubMed][Green Version]
  225. Liang, Y.; Song, X.; Li, Y.; Ma, T.; Su, P.; Guo, R.; Chen, B.; Zhang, H.; Sang, Y.; Liu, Y.; et al. Targeting the circBMPR2/miR-553/USP4 Axis as a Potent Therapeutic Approach for Breast Cancer. Mol. Ther. Nucleic Acids 2019, 17, 347–361. [Google Scholar] [CrossRef] [PubMed][Green Version]
  226. Rongna, A.; Yu, P.; Hao, S.; Li, Y. MiR-876-5p suppresses cell proliferation by targeting Angiopoietin-1 in the psoriasis. Biomed. Pharmacother. 2018, 103, 1163–1169. [Google Scholar] [CrossRef]
  227. Pei, X.; Li, Y.; Zhu, L.; Zhou, Z. Astrocyte-derived exosomes transfer miR-190b to inhibit oxygen and glucose deprivation-induced autophagy and neuronal apoptosis. Cell Cycle 2020, 19, 906–917. [Google Scholar] [CrossRef] [PubMed]
  228. Xie, Q.; Li, F.; Shen, K.; Luo, C.; Song, G. LOXL1-AS1/miR-515-5p/STAT3 Positive Feedback Loop Facilitates Cell Proliferation and Migration in Atherosclerosis. J. Cardiovasc. Pharmacol. 2020, 76, 151–158. [Google Scholar] [CrossRef] [PubMed]
  229. He, X.; Ji, J.; Wang, T.; Wang, M.B.; Chen, X.L. Upregulation of Circulating miR-195-3p in Heart Failure. Cardiology 2017, 138, 107–114. [Google Scholar] [CrossRef] [PubMed]
  230. Li, C.; Han, H.; Li, X.; Wu, J.; Li, X.; Niu, H.; Li, W. Analysis of lncRNA, miRNA, and mRNA Expression Profiling in Type i IFN and Type II IFN Overexpressed in Porcine Alveolar Macrophages. Int. J. Genomics 2021, 2021, 6666160. [Google Scholar] [CrossRef] [PubMed]
  231. Zhang, X.; Gu, H.; Wang, L.; Huang, F.; Cai, J. MiR-885-3p is down-regulated in peripheral blood mononuclear cells from T1D patients and regulates the inflammatory response via targeting TLR4/NF-κB signaling. J. Gene Med. 2020, 22, 3145. [Google Scholar] [CrossRef]
  232. Liao, C.H.; Liu, Y.; Wu, Y.F.; Zhu, S.W.; Cai, R.Y.; Zhou, L.; Yin, X.M. microRNA-329 suppresses epithelial-to-mesenchymal transition and lymph node metastasis in bile duct cancer by inhibiting laminin subunit beta 3. J. Cell. Physiol. 2019, 234, 17786–17799. [Google Scholar] [CrossRef]
  233. Wang, W.; Zhao, E.; Yu, Y.; Geng, B.; Zhang, W.; Li, X. MiR-216a exerts tumor-suppressing functions in renal cell carcinoma by targeting TLR4. Am. J. Cancer Res. 2018, 8, 476–488. [Google Scholar]
  234. Goodwin, A.J.; Li, P.; Halushka, P.V.; Cook, J.A.; Sumal, A.S.; Fan, H. Circulating miRNA 887 is differentially expressed in ARDS and modulates endothelial function. Am. J. Physiol. Lung Cell. Mol. Physiol. 2020, 318, L1261–L1269. [Google Scholar] [CrossRef] [PubMed]
  235. Guo, W.; Li, W.; Yuan, L.; Mei, X.; Hu, W. MicroRNA-106a-3p induces apatinib resistance and activates Janus-Activated Kinase 2 (JAK2)/Signal Transducer and Activator of Transcription 3 (STAT3) by targeting the SOCS system in gastric cancer. Med. Sci. Monit. 2019, 25, 10122–10128. [Google Scholar] [CrossRef] [PubMed]
  236. Zhao, X.; Li, D.; Zhao, S.T.; Zhang, Y.; Xu, A.; Hu, Y.Y.; Fang, Z. MiRNA-616 aggravates the progression of bladder cancer by regulating cell proliferation, migration and apoptosis through downregulating SOX7. Eur. Rev. Med. Pharmacol. Sci. 2019, 23, 9304–9312. [Google Scholar] [CrossRef] [PubMed]
  237. Song, Y.H.; Wang, J.; Nie, G.; Chen, Y.J.; Li, X.; Jiang, X.; Cao, W.H. MicroRNA-509-5p functions as an anti-oncogene in breast cancer via targeting SOD2. Eur. Rev. Med. Pharmacol. Sci. 2017, 21, 3617–3625. [Google Scholar] [CrossRef]
  238. Siege, S.R.; MacKenzie, J.; Chaplin, G.; Jablonski, N.G.; Griffiths, L. Circulating microRNAs involved in multiple sclerosis. Mol. Biol. Rep. 2012, 39, 6219–6225. [Google Scholar] [CrossRef]
  239. Magenta, A.; Cencioni, C.; Fasanaro, P.; Zaccagnini, G.; Greco, S.; Sarra-Ferraris, G.; Antonini, A.; Martelli, F.; Capogrossi, M.C. MiR-200c is upregulated by oxidative stress and induces endothelial cell apoptosis and senescence via ZEB1 inhibition. Cell Death Differ. 2011, 18, 1628–1639. [Google Scholar] [CrossRef][Green Version]
  240. Chen, Y.; Li, Y.; Gao, H. Long noncoding RNA CASC9 promotes the proliferation and metastasis of papillary thyroid cancer via sponging miR-488-3p. Cancer Med. 2020, 9, 1830–1841. [Google Scholar] [CrossRef][Green Version]
  241. Shibayama, Y.; Kubo, Y.; Nakagawa, T.; Iseki, K. MicroRNA-101-5p suppresses the expression of the ras-related protein RAP1A. Biol. Pharm. Bull. 2019, 42, 1332–1336. [Google Scholar] [CrossRef][Green Version]
  242. Chhabra, R. Let-7i-5p, miR-181a-2-3p and EGF/PI3K/SOX2 axis coordinate to maintain cancer stem cell population in cervical cancer. Sci. Rep. 2018, 18, 7840. [Google Scholar] [CrossRef][Green Version]
  243. Li, Y.; Wu, Y.; Sun, Z.; Wang, R.; Ma, D. MicroRNA-376a inhibits cell proliferation and invasion in glioblastoma multiforme by directly targeting specificity protein 1. Mol. Med. Rep. 2018, 17, 1583–1590. [Google Scholar] [CrossRef]
  244. Tang, C.; Wang, X.; Ji, C.; Zheng, W.; Yu, Y.; Deng, X.; Zhou, X.; Fang, L. The Role of miR-640: A Potential Suppressor in Breast Cancer via Wnt7b/β-catenin Signaling Pathway. Front. Oncol. 2021, 11, 1142. [Google Scholar] [CrossRef] [PubMed]
  245. Liang, D.; Wu, X.; Bai, J.; Zhang, L.; Yin, C.; Zhong, W. MiR-300 inhibits invasion and metastasis of osteosarcoma cell MG63 by negatively regulating PTTG1. Nan Fang Yi Ke Da Xue Xue Bao 2021, 41, 285–291. [Google Scholar] [CrossRef] [PubMed]
  246. Pan, Y.; Robertson, G.; Pedersen, L.; Lim, E.; Hernandez-Herrera, A.; Rowat, A.C.; Patil, S.L.; Chan, C.K.; Wen, Y.; Zhang, X.; et al. miR-509-3p is clinically significant and strongly attenuates cellular migration and multi-cellular spheroids in ovarian cancer. Oncotarget 2016, 7, 25930. [Google Scholar] [CrossRef] [PubMed]
  247. Xiao, W.; Yao, E.; Zheng, W.; Tian, F.; Tian, L. miR-337 can be a key negative regulator in melanoma. Cancer Biol. Ther. 2017, 18, 392–399. [Google Scholar] [CrossRef][Green Version]
  248. Gao, X.; Xu, D.; Li, S.; Wei, Z.; Li, S.; Cai, W.; Mao, N.; Jin, F.; Li, Y.; Yi, X.; et al. Pulmonary Silicosis Alters MicroRNA Expression in Rat Lung and miR-411-3p Exerts Anti-fibrotic Effects by Inhibiting MRTF-A/SRF Signaling. Mol. Ther. Nucleic Acids 2020, 20, 851–865. [Google Scholar] [CrossRef]
  249. Lemecha, M.; Morino, K.; Imamura, T.; Iwasaki, H.; Ohashi, N.; Ida, S.; Sato, D.; Sekine, O.; Ugi, S.; Maegawa, H. MiR-494-3p regulates mitochondrial biogenesis and thermogenesis through PGC1-α signalling in beige adipocytes. Sci. Rep. 2018, 8, 15096. [Google Scholar] [CrossRef][Green Version]
  250. Yu, D.; Liu, X.; Han, G.; Liu, Y.; Zhao, X.; Wang, D.; Bian, X.; Gu, T.; Wen, L. The let-7 family of microRNAs suppresses immune evasion in head and neck squamous cell carcinoma by promoting PD-L1 degradation. Cell Commun. Signal. 2019, 17, 173. [Google Scholar] [CrossRef][Green Version]
  251. Lin, W.; Tang, Y.; Zhao, Y.; Zhao, J.; Zhang, L.; Wei, W.; Chen, J. MiR-144-3p Targets FoxO1 to Reduce Its Regulation of Adiponectin and Promote Adipogenesis. Front. Genet. 2020, 11, 603144. [Google Scholar] [CrossRef]
  252. Sheedy, P.; Medarova, Z. The fundamental role of miR-10b in metastatic cancer. Am. J. Cancer Res. 2018, 8, 1674–1688. [Google Scholar]
  253. Gao, C.; Wei, J.; Tang, T.; Huang, Z. Role of microRNA-33a in malignant cells (review). Oncol. Lett. 2020, 20, 2537–2556. [Google Scholar] [CrossRef]
  254. Lin, Y.; Dan, H.; Lu, J. Overexpression of microRNA-136-3p Alleviates Myocardial Injury in Coronary Artery Disease via the Rho A/ROCK Signaling Pathway. Kidney Blood Press. Res. 2020, 45, 477–496. [Google Scholar] [CrossRef] [PubMed]
  255. Wang, H.; Deng, Q.; Lv, Z.; Ling, Y.; Hou, X.; Chen, Z.; Dinglin, X.; Ma, S.; Li, D.; Wu, Y.; et al. N6-methyladenosine induced miR-143-3p promotes the brain metastasis of lung cancer via regulation of VASH1. Mol. Cancer 2019, 18, 181. [Google Scholar] [CrossRef] [PubMed][Green Version]
  256. Qiang, Z.; Jin, B.; Peng, Y.; Zhang, Y.; Wang, J.; Chen, C.; Wang, X.; Liu, F. miR-762 modulates thyroxine-induced cardiomyocyte hypertrophy by inhibiting Beclin-1. Endocrine 2019, 66, 585–595. [Google Scholar] [CrossRef] [PubMed]
  257. Li, S.; Hou, X.; Wu, C.; Han, L.; Li, Q.; Wang, J.; Luo, S. MiR-645 promotes invasiveness, metastasis and tumor growth in colorectal cancer by targeting EFNA5. Biomed. Pharmacother. 2020, 125, 109889. [Google Scholar] [CrossRef]
  258. Xia, L.H.; Yan, Q.H.; Sun, Q.D.; Gao, Y.P. MiR-411-5p acts as a tumor suppressor in non-small cell lung cancer through targeting PUM1. Eur. Rev. Med. Pharmacol. Sci. 2018, 22, 5546–5553. [Google Scholar] [CrossRef]
  259. Chakrabarti, M.; Ray, S.K. Anti-tumor activities of luteolin and silibinin in glioblastoma cells: Overexpression of miR-7-1-3p augmented luteolin and silibinin to inhibit autophagy and induce apoptosis in glioblastoma in vivo. Apoptosis 2016, 21, 312–328. [Google Scholar] [CrossRef]
  260. Liu, F.; Zhang, H.; Xie, F.; Tao, D.; Xiao, X.; Huang, C.; Wang, M.; Gu, C.; Zhang, X.; Jiang, G. Hsa_circ_0001361 promotes bladder cancer invasion and metastasis through miR-491-5p/MMP9 axis. Oncogene 2020, 39, 1696–1709. [Google Scholar] [CrossRef]
  261. Yu, T.; Wang, L.N.; Li, W.; Zuo, Q.F.; Li, M.M.; Zou, Q.M.; Xiao, B. Downregulation of miR-491-5p promotes gastric cancer metastasis by regulating SNAIL and FGFR4. Cancer Sci. 2018, 109, 1393–1403. [Google Scholar] [CrossRef][Green Version]
  262. Li, J.; Lin, T.Y.; Chen, L.; Liu, Y.; Dian, M.J.; Hao, W.C.; Lin, X.L.; Li, X.Y.; Li, Y.L.; Lian, M.; et al. Mir-19 regulates the expression of interferon-induced genes and mhc class i genes in human cancer cells. Int. J. Med. Sci. 2020, 17, 953. [Google Scholar] [CrossRef][Green Version]
  263. Zhang, J.; Gao, D.; Zhang, H. Upregulation of miR-614 promotes proliferation and inhibits apoptosis in ovarian cancer by suppressing PPP2R2A expression. Mol. Med. Rep. 2018, 17, 6285–6292. [Google Scholar] [CrossRef]
  264. Gu, Y.; Cheng, Y.; Song, Y.; Zhang, Z.; Deng, M.; Wang, C.; Zheng, G.; He, Z. MicroRNA-493 suppresses tumor growth, invasion and metastasis of lung cancer by regulating E2F1. PLoS ONE 2014, 9, 102602. [Google Scholar] [CrossRef] [PubMed]
  265. Cimmino, A.; Calin, G.A.; Fabbri, M.; Iorio, M.V.; Ferracin, M.; Shimizu, M.; Wojcik, S.E.; Aqeilan, R.I.; Zupo, S.; Dono, M.; et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc. Natl. Acad. Sci. USA 2005, 102, 13944–13949. [Google Scholar] [CrossRef] [PubMed][Green Version]
  266. Liu, Y.; Li, J.; Li, M.; Li, F.; Shao, Y.; Wu, L. microRNA-510-5p promotes thyroid cancer cell proliferation, migration, and invasion through suppressing SNHG15. J. Cell. Biochem. 2019, 120, 11738–11744. [Google Scholar] [CrossRef] [PubMed]
  267. Zhao, X.; Liu, S.; Yan, B.; Yang, J.; Chen, E. Mir-581/smad7 axis contributes to colorectal cancer metastasis: A bioinformatic and experimental validation-based study. Int. J. Mol. Sci. 2020, 21, 6499. [Google Scholar] [CrossRef]
  268. Ren, K.; Yu, Y.; Wang, X.; Liu, H.; Zhao, J. MiR-340-3p-HUS1 axis suppresses proliferation and migration in lung adenocarcinoma cells. Life Sci. 2021, 274, 119330. [Google Scholar] [CrossRef]
  269. Monteleone, N.J.; Lutz, C.S. miR-708-5p: A microRNA with emerging roles in cancer. Oncotarget 2017, 8, 71292–71316. [Google Scholar] [CrossRef][Green Version]
  270. Ramírez-Salazar, E.G.; Almeraya, E.V.; López-Perez, T.V.; Patiño, N.; Salmeron, J.; Velázquez-Cruz, R. MicroRNA-548-3p overexpression inhibits proliferation, migration and invasion in osteoblast-like cells by targeting STAT1 and MAFB. J. Biochem. 2020, 168, 203–211. [Google Scholar] [CrossRef]
  271. Shi, J.; Gong, L.; Chen, L.; Luo, J.; Song, G.; Xu, J.; Lv, Z.; Tao, H.; Xia, Y.; Ye, Z. miR-618 Suppresses Metastasis in Gastric Cancer by Downregulating the Expression of TGF-β2. Anat. Rec. 2019, 302, 931–940. [Google Scholar] [CrossRef]
  272. Sun, Y.; Zhao, J.; Yin, X.; Yuan, X.; Guo, J.; Bi, J. miR-297 acts as an oncogene by targeting GPC5 in lung adenocarcinoma. Cell Prolif. 2016, 49, 636–643. [Google Scholar] [CrossRef]
  273. Yao, Y.; Jia, H.; Wang, G.; Ma, Y.; Sun, W.; Li, P. MiR-297 protects human umbilical vein endothelial cells against LPS-induced inflammatory response and apoptosis. Cell. Physiol. Biochem. 2019, 52, 696–707. [Google Scholar] [CrossRef]
  274. Liu, Z.; Lu, X.; Wen, L.; You, C.; Jin, X.; Liu, J. Hsa_circ_0014879 regulates the radiosensitivity of esophageal squamous cell carcinoma through miR-519-3p/CDC25A axis. Anticancer. Drugs 2021, 33, e349–e361. [Google Scholar] [CrossRef] [PubMed]
  275. Zhang, X.L.; An, B.F.; Zhang, G.C. MiR-27 alleviates myocardial cell damage induced by hypoxia/reoxygenation via targeting TGFBR1 and inhibiting NF-κB pathway. Kaohsiung J. Med. Sci. 2019, 35, 607–614. [Google Scholar] [CrossRef] [PubMed]
  276. Qian, F.H.; Deng, X.; Zhuang, Q.X.; Wei, B.; Zheng, D.D. MiR-625-5p suppresses inflammatory responses by targeting AKT2 in human bronchial epithelial cells. Mol. Med. Rep. 2019, 19, 1951–1957. [Google Scholar] [CrossRef] [PubMed][Green Version]
  277. Yoshida, K.; Yokoi, A.; Yamamoto, Y.; Kajiyama, H. ChrXq27.3 miRNA cluster functions in cancer development. J. Exp. Clin. Cancer Res. 2021, 40, 1–11. [Google Scholar] [CrossRef] [PubMed]
  278. Lv, P.; Luo, Y.F.; Zhou, W.Y.; Liu, B.; Zhou, Z.; Shi, Y.Z.; Huang, R.; Peng, C.; He, Z.L.; Wang, J.; et al. miR-373 inhibits autophagy and further promotes apoptosis of cholangiocarcinoma cells by targeting ULK1. Kaohsiung J. Med. Sci. 2020, 36, 429–440. [Google Scholar] [CrossRef] [PubMed][Green Version]
  279. Chen, T.; Qin, S.; Gu, Y.; Pan, H.; Bian, D. Long non-coding RNA NORAD promotes the occurrence and development of non-small cell lung cancer by adsorbing MiR-656-3p. Mol. Genet. Genomic Med. 2019, 7, e757. [Google Scholar] [CrossRef] [PubMed][Green Version]
  280. He, W.; Cheng, Y. Inhibition of miR-20 promotes proliferation and autophagy in articular chondrocytes by PI3K/AKT/mTOR signaling pathway. Biomed. Pharmacother. 2018, 97, 607–615. [Google Scholar] [CrossRef]
  281. Zhang, Y.; Dai, J.; Tang, J.; Zhou, L.; Zhou, M. MicroRNA-649 promotes HSV-1 replication by directly targeting MALT1. J. Med. Virol. 2017, 89, 1069–1079. [Google Scholar] [CrossRef]
  282. Pepe, F.; Visone, R.; Veronese, A. The glucose-regulated MiR-483-3p influences key signaling pathways in cancer. Cancers 2018, 10, 181. [Google Scholar] [CrossRef][Green Version]
  283. Lu, J.; Zhou, L.; Wu, B.; Duan, Y.; Sun, Y.; Gu, L.; Xu, D.; Du, C. MiR-501-3p functions as a tumor suppressor in non-small cell lung cancer by downregulating RAP1A. Exp. Cell Res. 2020, 387, 111752. [Google Scholar] [CrossRef]
  284. Zhang, D.; Yang, N. MiR-335-5p inhibits cell proliferation, migration and invasion in colorectal cancer through downregulating LDHB. J. Buon 2019, 24, 1128–1136. [Google Scholar] [PubMed]
  285. Gracia-Cazaña, T.; González, S.; Parrado, C.; Juarranz, Á.; Gilaberte, Y. Influence of the Exposome on Skin Cancer. Actas Dermosifiliogr. 2020, 111, 460–470. [Google Scholar] [CrossRef] [PubMed]
  286. Pecorelli, A.; Cordone, V.; Messano, N.; Zhang, C.; Falone, S.; Amicarelli, F.; Hayek, J.; Valacchi, G. Altered inflammasome machinery as a key player in the perpetuation of Rett syndrome oxinflammation. Redox Biol. 2020, 28, 101334. [Google Scholar] [CrossRef] [PubMed]
  287. Valacchi, G.; Sticozzi, C.; Pecorelli, A.; Cervellati, F.; Cervellati, C.; Maioli, E. Cutaneous responses to environmental stressors. Ann. N. Y. Acad. Sci. 2012, 1271, 75–81. [Google Scholar] [CrossRef] [PubMed]
  288. Valacchi, G.; Virgili, F.; Cervellati, C.; Pecorelli, A. OxInflammation: From subclinical condition to pathological biomarker. Front. Physiol. 2018, 9, 858. [Google Scholar] [CrossRef] [PubMed][Green Version]
  289. Vierkötter, A.; Schikowski, T.; Ranft, U.; Sugiri, D.; Matsui, M.; Krämer, U.; Krutmann, J. Airborne particle exposure and extrinsic skin aging. J. Investig. Dermatol. 2010, 130, 2719–2726. [Google Scholar] [CrossRef][Green Version]
  290. Magnani, N.D.; Muresan, X.M.; Belmonte, G.; Cervellati, F.; Sticozzi, C.; Pecorelli, A.; Miracco, C.; Marchini, T.; Evelson, P.; Valacchi, G. Skin damage mechanisms related to airborne particulate matter exposure. Toxicol. Sci. 2016, 149, 227–236. [Google Scholar] [CrossRef] [PubMed][Green Version]
  291. Furukawa, J.Y.; Martinez, R.M.; Morocho-Jácome, A.L.; Castillo-Gómez, T.S.; Pereda-Contreras, V.J.; Rosado, C.; Velasco, M.V.R.; Baby, A.R. Skin impacts from exposure to ultraviolet, visible, infrared, and artificial lights—A review. J. Cosmet. Laser Ther. 2021, 23, 1–7. [Google Scholar] [CrossRef]
  292. Pattison, D.I.; Davies, M.J. Actions of ultraviolet light on cellular structures. EXS 2006, 96, 131–157. [Google Scholar] [CrossRef]
  293. Svobodova, A.; Walterova, D.; Vostalova, J. Ultraviolet light induced alteration to the skin. Biomed. Pap. Med. Fac. Univ. Palacky. Olomouc. Czech. Repub. 2006, 150, 25–38. [Google Scholar] [CrossRef][Green Version]
  294. Fritsche, K. Important differences exist in the dose-response relationship between diet and immune cell fatty acids in humans and rodents. Lipids 2007, 42, 961–979. [Google Scholar] [CrossRef] [PubMed]
  295. Xu, J.; Li, C.X.; Li, Y.S.; Lv, J.Y.; Ma, Y.; Shao, T.T.; Xu, L.D.; Wang, Y.Y.; Du, L.; Zhang, Y.P.; et al. MiRNA-miRNA synergistic network: Construction via co-regulating functional modules and disease miRNA topological features. Nucleic Acids Res. 2011, 39, 825–836. [Google Scholar] [CrossRef] [PubMed][Green Version]
  296. Fry, R.C.; Rager, J.E.; Bauer, R.; Sebastian, E.; Peden, D.B.; Jaspers, I.; Alexis, N.E. Air toxics and epigenetic effects: Ozone altered microRNAs in the sputum of human subjects. Am. J. Physiol. Lung Cell. Mol. Physiol. 2014, 306, L1129–L1137. [Google Scholar] [CrossRef] [PubMed][Green Version]
  297. Abdel-Shafy, H.I.; El-Khateeb, M.A.; Mansour, M.S.M. Treatment of leather industrial wastewater via combined advanced oxidation and membrane filtration. Water Sci. Technol. 2016, 74, 586–594. [Google Scholar] [CrossRef] [PubMed]
  298. Izzotti, A.; Calin, G.A.; Arrigo, P.; Steele, V.E.; Croce, C.M.; De Flora, S. Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke. FASEB J. 2009, 23, 806–812. [Google Scholar] [CrossRef] [PubMed]
  299. Izzotti, A.; Pulliero, A. The effects of environmental chemical carcinogens on the microRNA machinery. Int. J. Hyg. Environ. Health 2014, 217, 601–627. [Google Scholar] [CrossRef] [PubMed]
  300. Huang, Y.; Unger, N.; Harper, K.; Heyes, C. Global Climate and Human Health Effects of the Gasoline and Diesel Vehicle Fleets. GeoHealth 2020, 4, e2019GH000240. [Google Scholar] [CrossRef]
  301. Izzotti, A.; Pulliero, A. Molecular damage and lung tumors in cigarette smoke-exposed mice. Ann. N. Y. Acad. Sci. 2015, 1340, 75–83. [Google Scholar] [CrossRef]
  302. Meek, M.D. Ah receptor and estrogen receptor-dependent modulation of gene expression by extracts of diesel exhaust particles. Environ. Res. 1998, 79, 114–121. [Google Scholar] [CrossRef]
  303. Hoskin, R.; Pambianchi, E.; Pecorelli, A.; Grace, M.; Therrien, J.P.; Valacchi, G.; Lila, M.A. Novel spray dried algae-rosemary particles attenuate pollution-induced skin damage. Molecules 2021, 26, 3781. [Google Scholar] [CrossRef]
  304. Izzotti, A.; Calin, G.A.; Steele, V.E.; Croce, C.M.; De Flora, S. Relationships of microRNA expression in mouse lung with age and exposure to cigarette smoke and light. FASEB J. 2009, 23, 3243–3250. [Google Scholar] [CrossRef] [PubMed][Green Version]
Figure 1. Line plot analysis of the overall expression of the 2549 human miRNAs analyzed under each experimental condition tested. The expression of 2549 human miRNAs was evaluated at 0 and 24 h in skin either unexposed (Air) or exposed to diesel, ozone, and UV. miRNAs are distributed in horizontal lines according to their level of expression, the majority being located at intermediate levels of expression (central part of the distribution), and the minority being located at high and low levels of expression (lower and upper part of the distribution). The distribution profile is progressively modified according to the treatment used.
Figure 1. Line plot analysis of the overall expression of the 2549 human miRNAs analyzed under each experimental condition tested. The expression of 2549 human miRNAs was evaluated at 0 and 24 h in skin either unexposed (Air) or exposed to diesel, ozone, and UV. miRNAs are distributed in horizontal lines according to their level of expression, the majority being located at intermediate levels of expression (central part of the distribution), and the minority being located at high and low levels of expression (lower and upper part of the distribution). The distribution profile is progressively modified according to the treatment used.
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Figure 2. Scatter plot analysis of changes in miRNA-expression in human skin upon exposure to diesel, ozone, and UV at different times (0 and 24 h).
Figure 2. Scatter plot analysis of changes in miRNA-expression in human skin upon exposure to diesel, ozone, and UV at different times (0 and 24 h).
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Figure 3. Bidimensional principal component analysis (PCA) of miRNA profiles of skin samples either untreated (air) or treated with diesel, ozone, and UV at 0 (left panel) and 24 h (right panel). PCA1 (X axis), PCA2 (Y axis).
Figure 3. Bidimensional principal component analysis (PCA) of miRNA profiles of skin samples either untreated (air) or treated with diesel, ozone, and UV at 0 (left panel) and 24 h (right panel). PCA1 (X axis), PCA2 (Y axis).
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Figure 4. Hierarchical Cluster Analysis (HCA) reporting the expression of the 2549 miRNAs (colored horizontal bars) tested at time 0 (left panel) and 24 h (right panel) in samples either untreated (air) or treated with pollutants (ozone, diesel, and UV). Columns report miRNA expression profiles for each experimental condition. Similar expression profiles are linked in the upper hierarchical tree (green), thus being located nearby, while different expression profiles are located far away in the hierarchical tree.
Figure 4. Hierarchical Cluster Analysis (HCA) reporting the expression of the 2549 miRNAs (colored horizontal bars) tested at time 0 (left panel) and 24 h (right panel) in samples either untreated (air) or treated with pollutants (ozone, diesel, and UV). Columns report miRNA expression profiles for each experimental condition. Similar expression profiles are linked in the upper hierarchical tree (green), thus being located nearby, while different expression profiles are located far away in the hierarchical tree.
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Table 1. Diesel.
Table 1. Diesel.
MicroRNAFold ChangeFunctionReference
hsa-miR-495-5p>10Promotes Th2 differentiation in allergic rhinitis, as a tumor suppressor[23]
hsa-miR-628-5p>10Inhibits osteoblast differentiation via RUNX2[24]
hsa-miR-361-3p>10Suppresses proliferation, invasion inhibited cells invasive and proliferative abilities, and cell lines invasion and proliferation[25,26]
hsa-miR-875-5p>10Promotes cellular apoptosis and proliferation[27]
hsa-miR-509-3p>10Tumor suppressor[28,29]
hsa-miR-518b>10Suppresses cell proliferation, invasiveness, and migration in colorectal cancer[30,31]
hsa-miR-516b-5p>10Cell proliferation, inducing G1 cell cycle arrest and apoptosis[32]
hsa-miR-381-5p>10Induces apoptosis[33]
hsa-miR-661>10Promotes proliferation, migration, and metastasis of NSCLC[34]
hsa-miR-216a-3p>10Antitumor functions[35]
hsa-miR-548c-3p>10Inflammatory responses and potential estrogen receptor sensitivity[36]
hsa-miR-106a-3p>10Cell proliferation and autophagy[37]
hsa-miR-616-5p>10Promotes angiogenesis and modulates cell proliferation[38]
hsa-miR-671-3p>10Suppresses proliferation and invasion of breast cancer cells and regulates metabolic processes[39,40]
hsa-miR-544a>10Regulates migration and invasion in colorectal cancer cells[41]
hsa-miR-614>10Inflammatory process[42]
hsa-miR-525-3p<10Modifies the expression of proinflammatory cytokines; apoptosis[43]
hsa-miR-378c<10Regulates the angiogenic capacity of CD34(+) progenitor cells[44]
hsa-miR-924<10Suppresses the proliferation, migration, and invasion of NSCLC cells[45]
hsa-miR-522-3p<10Cell proliferation of human glioblastoma cells; modulates the expression of proinflammatory cytokines[46]
hsa-miR-431-5p<10Promotes differentiation and regeneration of cells[47,48]
hsa-miR-770-5p<10Suppresses cell apoptosis and the release of proinflammatory factors[49]
hsa-miR-183-5p<10Tumor suppressor inflammation and alters miRNA expression in the airway epithelium[50]
hsa-miR-598-5p<10Promotes cell proliferation and cell cycle progression in human colorectal carcinoma; elevates apoptosis[51]
hsa-miR-486-5p<10Regulation of heart contraction, muscle contraction, and ion channel activity[52]
hsa-miR-125a-5p<10Regulates stress response, apoptosis, proliferation, angiogenesis, and expression of genes, associated with human lung cancer[53]
hsa-miR-34b-5p<10Regulates stress response, apoptosis, proliferation, angiogenesis, and expression of genes, and is upregulated during cardiac hypertrophy[54]
hsa-miR-301a-3p<10Promotes autophagy and inhibits apoptosis[55,56]
hsa-miR-23c<10Inhibits cell proliferation and induces apoptosis of hepatocellular carcinoma cells; cell growth arrest and apoptosis.[57]
hsa-miR-383-5p<10Oxidative stress and inflammation-related factors[58]
hsa-miR-574-5p<10Promotes the differentiation of human cardiac fibroblasts[59]
hsa-miR-151a-5p<10Regulation of cellular respiration and ATP production through targeting Cytb[60]
hsa-miR-514a-3p<10Attenuates proliferation and increases chemoresistance[61]
hsa-miR-136-3p<10Promotes apoptosis in gastric cancer cells[62]
hsa-miR-1-3p<10Inflammation; regulator of heart adaption after ischemia or ischemic stress[63]
hsa-miR-18a-3p<10Downregulated in aging cells; induces the apoptosis of colon cancer cells[64]
hsa-miR-502-5p<10Enhances early apoptosis and inhibits proliferation of breast cancer cells[65]
hsa-miR-451a<10Apoptosis; inhibits autophagy[66]
hsa-miR-19b-1-5p<10Linked to oxidative stress, inflammation, and atherosclerosis[67]
hsa-miR-873-5p<0.1Tumor suppressor in thyroid cancer by inhibiting the proliferation, migration, and invasion of the cancer cells[68]
hsa-miR-212-5p<0.1Promotes cancer cell apoptosis and suppresses cancer cell proliferation and invasion[69]
hsa-miR-552-5p<0.1Tumorigenesis; progression[70]
hsa-let-7a-3p<0.1Linked to oxidative stress, inflammation, and atherosclerosis[71]
hsa-miR-495-3p<0.1Regulates proliferation, apoptosis, migration, and invasion in metastatic prostate cancer cells.[68]
hsa-miR-767-3p<0.1Promoted cell proliferation in human melanoma cell lines[72]
hsa-miR-27b-5p<0.1Involved in beige and brown adipogenesis after cold exposure[73]
hsa-miR-26a-2-3p<0.1Regulated stress response, apoptosis, proliferation, angiogenesis, and expression of genes[74]
hsa-miR-629-5p<0.1Action on tumor growth and metastasis in hepatocellular carcinoma[75]
hsa-miR-543<0.1Cell oxidative phosphorylation[76]
hsa-miR-515-5p<0.1Upregulated in placentas from women with preeclampsia[77]
hsa-miR-708-5p<0.1Induces apoptosis and suppresses tumorigenicity in renal cancer cells[78]
hsa-miR-378j<0.1Tumor suppressor[79]
hsa-miR-548az-3p<0.1Alters inflammation[80]
hsa-miR-876-5p<0.1Regulates regulation proliferation, migration, invasion, and glutaminolysis in gastric cancer cells[37]
hsa-miR-656-3p<0.1Suppresses glioma cell proliferation, neurosphere formation, migration, and invasion[81]
hsa-miR-944<0.1Increases p53 expression in cancer cells[82]
hsa-miR-518e-3p<0.1Tumor suppressor[83]
hsa-miR-373-3p<0.1Promotes the invasion and migration of breast cancer; regulates inflammatory cytokine-mediated chondrocyte proliferation[32]
Table 2. Ozone exposure.
Table 2. Ozone exposure.
MicroRNAFold ChangeFunctionReference
hsa-miR-628-5p>10Inhibits osteoblast differentiation[84]
hsa-miR-15a-3p>10Proliferation; inflammation; apoptosis[25,26]
hsa-miR-548am-3p>10Induces proliferation and migration[85]
hsa-miR-550b-2-5p>10Cancer promotion[86]
hsa-miR-495-5p>10Tumor suppressor; proliferation and differentiation of osteoblasts in mice; inhibits the growth of fibroblasts in hypertrophic scar[87]
hsa-miR-345-3p>10Apoptosis and inflammation[24,88]
hsa-miR-548q>10Induces proliferation and migration[89]
hsa-miR-887-3p>10Pathways in cancer[86]
hsa-miR-877-5p>10Pathways in cancer[90]
hsa-miR-513c-5p>10Pathways in cancer[91]
hsa-miR-422a>10Pathways in cancer[92]
hsa-miR-194-5p>10Pathways in cancer[93]
hsa-miR-378b>10Inflammation and cell cycle[94]
hsa-miR-610>10Pathways in cancer[95]
hsa-miR-519e-5p>10Atherosclerosis and pathways in cancer[96]
hsa-miR-627-5p>10Cell proliferation and cancer promotion[97,98]
hsa-miR-548au-5p>10Pathways in cancer[99]
hsa-miR-770-5p>10Apoptosis and inflammation[100]
hsa-miR-196b-3p>10Cell proliferation[101]
hsa-miR-330-3p>10Apoptosis and cell proliferation[102]
hsa-miR-617>10Pathways in cancer[103]
hsa-miR-375>10Cell proliferation and pathways in cancer[104]
hsa-miR-936>10Cell proliferation, pathways in cancer, and apoptosis[105]
hsa-miR-657>10Inflammation[106]
hsa-miR-542-5p>10Mitochondrial dysfunction and inflammation[107]
hsa-miR-136-3p>10Vascularization and pathways in cancer[108]
hsa-miR-409-5p>10Cardiovascular process, proliferation, migration, and cell cycle.[109,110]
hsa-miR-154-3p>10Pathways in cancer[111,112]
hsa-miR-378c>10Proliferation and inhibited apoptosis[113]
hsa-miR-93-3p>10Inflammation and apoptosis[114]
hsa-miR-556-3p>10Cell proliferation and apoptosis[115]
hsa-miR-518c-5p>10Tumor suppressor[116]
hsa-miR-23b-5p>10Cell proliferation and cancer[32]
hsa-miR-504-5p>10Cell proliferation and differentiation[117]
hsa-miR-509-3p>10Cardiovascular process[118]
hsa-miR-514a-3p>10Tumor suppressor[119]
hsa-miR-431-5p>10Cell proliferation and apoptosis[120]
hsa-miR-506-3p>10Cell proliferation and cancer[121]
hsa-miR-645>10Cell proliferation and cancer[122]
hsa-miR-129-5p>10Inhibits the proliferation and metastasis of gastric cancer cells[123]
hsa-miR-516b-5p>10Migration, cell proliferation, and cancer process[124]
hsa-miR-512-3p>10Apoptosis and cell cycle[125]
hsa-miR-101-5p>10Apoptosis and promotes cell proliferation[126]
hsa-miR-561-5p>10Cell proliferation, G(1)/S transition, and suppresses apoptosis[127]
hsa-miR-194-5p>10Cell proliferation and cancer[128]
hsa-miR-329-3p>10Proliferation, invasion, and suppresses cell apoptosis[129]
hsa-let-7i-3p>10Coronary disease and cancer[130]
hsa-miR-129-2-3p>10Proliferation, invasion, and apoptosis[131]
hsa-miR-548a-5p>10Proliferation and inhibits apoptosis[132]
hsa-miR-887-5p>10Pathways in cancer[133]
hsa-miR-99a-3p>10Cell proliferation and pathways in cancer[134]
hsa-miR-487a-3p>10Cell proliferation and cancer[135]
hsa-miR-378g>10Cancer promotion[136]
hsa-miR-548at-5p>10Neurodegenerative disease[137]
hsa-miR-374c-5p>10Proliferation, apoptosis, and autophagy[138]
hsa-miR-106a-3p>10Proliferation and apoptosis[139]
hsa-miR-92a-2-5p>10Apoptosis and cell proliferation[140]
hsa-miR-616-5p>10Invasion, cell migration, and cancer[141]
hsa-miR-509-5p>10Tumor suppressor[142]
hsa-miR-598-3p>10Cancer process[21]
hsa-miR-873-5p>10Cell migration and cancer[143]
hsa-miR-525-3p<10Cancer cell migration[21]
hsa-miR-500a-5p<10Cell apoptosis and proliferation[144]
hsa-miR-659-3p<10Cell proliferation and cancer; apoptosis[145]
hsa-miR-526b-5p<10Cell proliferation and cancer[146]
hsa-miR-764<10Cardiac diseases and cancer[147]
hsa-miR-934<10Cancer progression and inflammation[148]
hsa-miR-516a-5p<10Cell proliferation and cancer[149]
hsa-miR-520f-3p<10DNA repair[150]
hsa-miR-369-5p<10Aerobic glycolysis and pathways in cancer[151]
hsa-miR-613<10Invasion and cell proliferation[152]
hsa-miR-411-3p<10Proliferation and cancer[153]
hsa-miR-432-3p<10Inflammation[154]
hsa-let-7c-3p<10Apoptosis[155]
hsa-miR-671-5p<10Proliferation and cell cycle[156]
hsa-miR-181d-5p<10Proliferation and angiogenesis[157]
hsa-miR-192-5p<10Hypertension and cancer[158]
hsa-let-7g-3p<10Linked to oxidative stress, inflammation, and atherosclerosis[159]
hsa-miR-1-3p<10Decreases tumor volume in a xenograft model[68]
hsa-miR-515-3p<10Cell proliferation, migration, invasion, and induced apoptosis[160]
hsa-miR-320d<10Apoptosis and cancer[161]
hsa-miR-548aa<10Can alter the inflammatory responses[162]
hsa-miR-502-5p<10Cell proliferation and invasion[37]
hsa-miR-758<10Proliferation and invasion[163]
hsa-miR-7-1-3p<10Autophagy and cancer process[164]
hsa-miR-324-3p<10Cell proliferation and cancer[165]
hsa-miR-520g-3p<10DNA repair[166]
hsa-miR-576-5p<10Cell invasion and cancer[151]
hsa-miR-520a-3p<10Inhibits tumor progression, indicating its potential role as a tumor suppressor.[167]
hsa-miR-449b-3p<10Proliferation[168]
hsa-miR-211-5p<10Pathways in cancer[169]
hsa-miR-376a-3p<10Coronary artery disease[170]
hsa-miR-939-3p<10Pathways in cancer[171]
hsa-miR-214-3p<10Inhibition of migration and proliferation[172]
hsa-miR-609<10Cardiovascular process[173]
hsa-miR-29a-5p<10Cardiac myocytes and overall cardiac dysfunction[174]
hsa-miR-449c-3p<10Inhibits NSCLC cell progression[175]
hsa-miR-185-3p<10Proliferation and invasion of cell[176]
hsa-miR-766-3p<10Suppresses apoptosis and facilitates autophagy[177]
hsa-miR-486-5p<10Regulation of heart contraction, muscle contraction, and ion channel activity[53]
hsa-miR-144<10Tumor inhibitors or tumor suppressors, proliferation, and apoptosis[53]
hsa-miR-664a-5p<10Induces cell differentiation[178]
hsa-miR-32-3p<10Atherosclerosis[179]
hsa-miR-224-3p<10Cell proliferation and promotes apoptosis[180]
hsa-miR-130a-5p<10Myocardial infarction[181]
hsa-miR-378i<10Metabolic pathways, mitochondrial energy homeostasis, and related biological processes[182]
hsa-miR-642b-5p<10Inflammation[183]
hsa-miR-668-3p<10Progression of different types of cancer[184]
hsa-miR-18b-5p<10Progression of different types of cancer; cardiac function[185]
hsa-miR-483-3p<10Apoptosis[186]
hsa-miR-485-3p<10Cell proliferation; pathways in cancer[187]
hsa-miR-200c-5p<10Oxidative stress and cell apoptosis[188]
hsa-miR-126-5p<10Linked to oxidative stress, inflammation, and atherosclerosis[189]
hsa-miR-26b-3p<10Cell proliferation and invasion[190]
hsa-miR-378d<10Proliferation and migration of cancer[191]
hsa-miR-526b-3p<10Regulates the proliferation, invasion, and migration of cancer cells[192]
hsa-miR-575<10Oncogene[193]
hsa-miR-564<10Cell proliferation and invasion[194]
hsa-miR-513a-5p<10Induced apoptosis[195]
hsa-miR-548i<10Downregulates the inflammatory cytokines[196]
hsa-miR-188-5p<10Cell proliferation and cancer promotion[197]
hsa-miR-563<10Cell proliferation and cancer promotion[198]
hsa-miR-139-3p<10Proliferation and invasion[199]
hsa-miR-34a-5p<0.1Inflammation[200]
hsa-miR-34b-5p<0.1P53 effector, cell proliferation, and apoptosis[201]
hsa-miR-371b-5p<0.1Cell proliferation and apoptosis[202]
hsa-let-7f-2-3p<0.1Cell proliferation and apoptosis[203,204]
hsa-miR-557<0.1Tumor suppressor[205]
hsa-miR-574-5p<0.1Cell cycle and cancer process[206]
hsa-miR-216a-3p<0.1Cell proliferation and apoptosis[207]
hsa-miR-466<0.1Tumor suppressor[208]
hsa-miR-222-3p<0.1Cell viability, migration, and invasion[209]
hsa-miR-586<0.1Cell proliferation, invasion, metastasis, and apoptosis[210]
hsa-miR-939-5p<0.1Inflammation[211]
hsa-miR-548b-3p<0.1Proliferation, apoptosis, and mitochondrial function[212]
hsa-miR-517c-3p<0.1Responses to stress; alterations in circulating glucose levels[213]
hsa-miR-630<0.1Oxidative damage and cell migration[214]
hsa-miR-544a<0.1Pathways in cancer[215]
hsa-miR-603<0.1Proliferation, migration, invasion, and metastasis[216]
hsa-miR-552-5p<0.1Cell proliferation[217]
hsa-miR-562<0.1Tumor suppressor[218]
hsa-miR-548<0.1Cancer cell proliferation, migration, and invasion[219]
hsa-miR-518a-<0.1Tumor suppressor[220]
hsa-miR-433-5p<0.1Cardiovascular process[32]
hsa-miR-138-5p<0.1Cardiac function and pathological damage[221]
hsa-miR-548ad-5p<0.1Cancer cell proliferation, migration, and invasion[222]
hsa-miR-450a-2-3p<0.1Cell proliferation and cancer[220]
hsa-miR-548av-3p<0.1Cancer cell proliferation, migration, and invasion[223]
hsa-miR-624-5p<0.1Cell proliferation and cancer[220]
hsa-miR-553<0.1Cell proliferation and cancer[224]
hsa-miR-876-5p<0.1Cell proliferation and cancer[225]
hsa-miR-190b<0.1Autophagy and cell cycle[226]
hsa-miR-26a-2-3p<0.1Cell cycle and cancer process[227]
hsa-miR-515-5p<0.1Cardiac function and proliferation cells[75]
hsa-miR-195-3p<0.1Cardiac function and proliferation cells[228]
hsa-miR-365b-5p<0.1Inflammation and cell proliferation[229]
Hsa-miR-885-3p<0.1Inflammation[230]
Table 3. UV exposure.
Table 3. UV exposure.
MicroRNAFold VariationFunctionsReference
hsa-miR-329-3p>10Inhibits cell proliferation in glioma cells[231]
hsa-miR-520g-5p>10DNA repair[232]
hsa-miR-216a->10Regulates the proliferation, apoptosis, migration, and invasion of lung cancer cells[151]
hsa-miR-548c-3p>10Cancer cell proliferation, migration, and invasion[233]
hsa-miR-129-2-3p>10Inhibits the proliferation and metastasis of gastric cancer cells[220]
hsa-miR-887-5p<10Pathways in cancer[124]
hsa-miR-106a-3p>10Involved in tumorigenesis and highly expressed in gastric cancer[234]
hsa-miR-616-5p>10Progression of bladder cancer by regulating cell proliferation, migration, and apoptosis[235]
hsa-miR-509-5p>10Tumor suppressive effects[236]
hsa-miR-648>10Post-transcriptional regulators of glioblastoma[237]
hsa-miR-378h>10Metabolic pathways, mitochondrial energy homeostasis, and angiogenic network in tumors[238]
hsa-miR-200c-5p>10Upregulated by oxidative stress and induces endothelial cell apoptosis[183]
hsa-miR-525-3p<10Pathways in cancer[239]
hsa-miR-488-3p<10Pathways in cancer[44]
hsa-miR-101-5p<10Regulates cell proliferation[240]
hsa-let-7g-3p<10Modulates inflammatory responses; pathways in cancer[241]
hsa-miR-376a-2-5p<10Pathways in cancer[242]
hsa-miR-640<10Pathways in cancer[243]
hsa-miR-300<10Controls stem cell function and inhibits differentiation[244]
hsa-miR-509-3p<10Pathways in cancer[245]
hsa-miR-548au-5p<10Pathways in cancer[246]
hsa-miR-337-3p<10Pathways in cancer[100]
hsa-miR-411-3p<10Pathways in cancer[247]
hsa-miR-494-3p<10Mitochondrial biogenesis and pathways in cancer[248]
hsa-let-7e-3p<10Pathways in cancer[249]
hsa-miR-144-3p<10Regulates adipogenesis and pathways in cancer[250]
hsa-miR-196b-3p<10Cell proliferation[251]
hsa-miR-10b-5p<10Pathways in cancer[102]
hsa-miR-33a-5p<10Associated with carcinogenesis[252]
hsa-miR-136-3p<10Cardiac function and pathological damage in myocardial tissue, cardiomyocyte apoptosis, oxidative stress, and inflammatory response[253]
hsa-miR-143-3p<10Pathways in cancer[254]
hsa-miR-762<10Modulates thyroxine-induced cardiomyocyte and pathways in cancer[255]
hsa-miR-582-5p<10Cell proliferation[256]
hsa-miR-645<10Cell proliferation and apoptosis[21]
hsa-miR-411-5p<10Cell proliferation and pathways in cancer[257]
hsa-miR-7-1-3p<10Inhibits autophagy and induces apoptosis in glioblastoma[258]
hsa-miR-18a-3p<10Progression of different types of cancer; cardiac function.[259]
hsa-miR-99a-3p<10Cell proliferation and pathways in cancer[186]
hsa-miR-491-5p<10Cell proliferation and pathways in cancer[135]
hsa-miR-19b-1-5p<10Pathways in cancer[260,261]
hsa-miR-614<10Cell proliferation and pathways in cancer[262]
hsa-miR-493-5p<0.1Cell proliferation[263]
hsa-miR-15b-3p<0.1Proliferation, inflammation, and apoptosis[264]
hsa-miR-510-5p<0.1Cell proliferation[265]
hsa-miR-485-5p<0.1Cell proliferation and pathways in cancer[266]
hsa-miR-581<0.1Induces proliferation and migration[188]
hsa-miR-340-3p<0.1Cell proliferation and pathways in cancer[267]
hsa-miR-708-5p<0.1Cell proliferation and pathways in cancer[268]
hsa-miR-548j-3p<0.1Induces proliferation and migration[269]
hsa-miR-618<0.1Cell proliferation and pathways in cancer[270]
hsa-miR-885-3p<0.1Inflammatory response and pathways in cancer[271]
hsa-miR-297<0.1Oncogene, inflammatory response, and apoptosis[231]
hsa-miR-518a-5p<0.1Tumor suppressor[272,273]
hsa-let-7f-2-3p<0.1Proliferation and apoptosis[32]
hsa-miR-519b-3p<0.1Radiosensitivity of radio-resistant cells and pathways in cancer[205]
hsa-miR-27b-5p<0.1Prevents atherosclerosis by inhibiting inflammatory responses[274]
hsa-miR-625-5p<0.1Inflammation and inhibits cardiac hypertrophy[275]
hsa-miR-548ah-5p<0.1Induces proliferation and migration[276]
hsa-miR-892c-3p<0.1Pathways in cancer[86]
hsa-miR-373-3p<0.1Inhibits autophagy[277]
hsa-miR-656-3p<0.1Induces proliferation and migration[278]
hsa-miR-20a-3p<0.1Proliferation and autophagy[279]
hsa-miR-518a-3p<0.1Tumor suppressor[280]
hsa-miR-649<0.1Pathways in cancer[32]
hsa-miR-483-3p<0.1Pathways in cancer and cardiac response[281]
hsa-miR-501-3p<0.1Cell proliferation, clonogenicity, migration, and invasion[282]
hsa-miR-335-5p<0.1Cell proliferation, migration, and invasion.[283]
hsa-miR-129-5p<0.1Proliferation, invasion, and apoptosis[284]
hsa-miR-34c-5p<0.1Proliferation and apoptosis[132]
hsa-miR-548ao-5p<0.1Promotes proliferation and inhibits apoptosis[202]
hsa-miR-624-5p<0.1Cell proliferation and pathways in cancer[133]
Table 4. Number of the miRNAs involved in the pathways deregulated by each pollutant tested. Only miRNAs demonstrated to be involved in the pathways are included.
Table 4. Number of the miRNAs involved in the pathways deregulated by each pollutant tested. Only miRNAs demonstrated to be involved in the pathways are included.
DieselOzoneUV
Apoptosis163612
Cell cycle72411
Inflammation11217
DNA repair142
Pathways in cancer237239
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