MicroRNA and Its Role in Human Health

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 31 October 2024 | Viewed by 6218

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Guest Editor
Department of Nursing, College of Nursing, Chung Hwa University of Medical Technology Taiwan, Tainan, Taiwan
Interests: rheumatic disease; microRNA expression; microRNA regulation; molecular mechanism; molecular therapy; molecular diagnosis
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Special Issue Information

Dear Colleagues,

MicroRNAs (miRs) are small, noncoding single-strand RNAs that impact human health. Emerging pieces of evidence indicate that miRs can be used as diagnostic or therapeutic agents, and in studying molecular mechanisms or novel signal pathways of the diseases. MiRs bind to the 3’-untranslated regions of the specific messenger RNAs that promote their degradation by perfect complementarity or translational repression by partial complementarity. Therefore, the target genes can be upregulated or downregulated according to the expression levels of the corresponding miRs in disease models. For these reasons, it will be intriguing to decipher the regulation or expression of novel miRs with the target genes. Regulation of miRs can be achieved by many techniques, including vector-based miR precursor or sponge, agomiR or antagomiR transfer, and knock-in or -out by CRISPR. High-throughput screening by miR array provides large-scale data mining to create disease associations. In this Special Issue, we aim to include a broad spectrum of disease models in which miRs and their target genes act as diagnostic, therapeutic, and pathogenic molecules. Original research articles and reviews are welcome. We look forward to receiving your contributions.

Dr. Shih-Yao Chen
Guest Editor

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Keywords

  • microRNA
  • disease models
  • disease associations
  • molecular mechanism
  • molecular diagnosis
  • molecular therapy

Published Papers (7 papers)

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Research

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13 pages, 396 KiB  
Article
miR-155 and miR-21 as Diagnostic and Therapeutic Biomarkers for Ulcerative Colitis: There Is Still a Long Way to Go
by Danusia Onisor, Olga Brusnic, Claudia Banescu, Claudia Carstea, Maria Sasaran, Mircea Stoian, Calin Avram, Adrian Boiceanu, Alina Boeriu and Daniela Dobru
Biomedicines 2024, 12(6), 1315; https://doi.org/10.3390/biomedicines12061315 - 13 Jun 2024
Viewed by 274
Abstract
(1) Elucidating the role of miRNAs (miRs) in ulcerative colitis may provide new insights into disease pathogenesis, diagnosis, treatment, and monitoring We aimed to investigate whether plasma levels of miR-21-5p and miR-155-5p may be used to differentiate between patients with organic disease such [...] Read more.
(1) Elucidating the role of miRNAs (miRs) in ulcerative colitis may provide new insights into disease pathogenesis, diagnosis, treatment, and monitoring We aimed to investigate whether plasma levels of miR-21-5p and miR-155-5p may be used to differentiate between patients with organic disease such as ulcerative colitis (UC) and Clostridioides difficile infection (CDI), and patients with functional disease such as irritable bowel syndrome with diarrhea (IBS-D). (2) Serological samples were collected to quantify miR-155 and -21 expression, which was carried out through quantitative real-time polymerase chain reaction (qRT-PCR), from 84 patients: 34 with acute UC (group 1), 17 with CDI (group 2), and 33 with IBS-D (control group). (3) In this study, we found that the expression levels of miR-155-5p were almost the same for the two conditions and the control group (UC: 4.22 ± 1.61, CDI: 3.94 ± 1.62, IBS-D: 4.26 ± 1.26), with no significant differences either for ΔCt- or for ΔΔCt-derived parameters (p = 0.74 and p = 0.73, respectively). For miR-21, ΔCt levels presented significantly higher values among the ulcerative colitis group (p < 0.01), but the most important expression fold change was noticed in patients with CDI (UC:4.11 ± 8,46, CDI: 4.94 ± 9.68, IBS-D: 2.83 ± 5.41). (4) Circulating miR-155 and miR-21 were upregulated in UC, CDI, and IBS-D, but differentiation was not possible among them. But their involvement in the pathogenesis of the three diseases makes them suitable for improving the accuracy of diagnosis and facilitating the development of personalized treatment strategies. Full article
(This article belongs to the Special Issue MicroRNA and Its Role in Human Health)
15 pages, 4692 KiB  
Article
RNA-Binding Protein Motifs Predict microRNA Secretion and Cellular Retention in Hypothalamic and Other Cell Types
by Wenyuan He and Denise D. Belsham
Biomedicines 2024, 12(4), 857; https://doi.org/10.3390/biomedicines12040857 - 12 Apr 2024
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Abstract
Cellular microRNAs (miRNAs) can be selectively secreted or retained, adding another layer to their critical role in regulating human health and disease. To date, select RNA-binding proteins (RBPs) have been proposed to be a mechanism underlying miRNA localization, but the overall relevance of [...] Read more.
Cellular microRNAs (miRNAs) can be selectively secreted or retained, adding another layer to their critical role in regulating human health and disease. To date, select RNA-binding proteins (RBPs) have been proposed to be a mechanism underlying miRNA localization, but the overall relevance of RBPs in systematic miRNA sorting remains unclear. This study profiles intracellular and small extracellular vesicles’ (sEVs) miRNAs in NPY-expressing hypothalamic neurons. These findings were corroborated by the publicly available sEV and intracellular miRNA profiles of white and brown adipocytes, endothelium, liver, and muscle from various databases. Using experimentally determined binding motifs of 93 RBPs, our enrichment analysis revealed that sEV-originating miRNAs contained significantly different RBP motifs than those of intracellularly retained miRNAs. Multiple RBP motifs were shared across cell types; for instance, RBM4 and SAMD4 are significantly enriched in neurons, hepatocytes, skeletal muscle, and endothelial cells. Homologs of both proteins physically interact with Argonaute1/2 proteins, suggesting that they play a role in miRNA sorting. Machine learning modelling also demonstrates that significantly enriched RBP motifs could predict cell-specific preferential miRNA sorting. Non-optimized machine learning modeling of the motifs using Random Forest and Naive Bayes in all cell types except WAT achieved an area under the receiver operating characteristic (ROC) curve of 0.77–0.84, indicating a high predictive accuracy. Given that the RBP motifs have a significant predictive power, these results underscore the critical role that RBPs play in miRNA sorting within mammalian cells and reinforce the importance of miRNA sequencing in preferential localization. For the future development of small RNA therapeutics, considering these RBP-RNA interactions could be crucial to maximize delivery effectiveness and minimize off-target effects. Full article
(This article belongs to the Special Issue MicroRNA and Its Role in Human Health)
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14 pages, 4153 KiB  
Article
Early Growth Response Protein 1 Exacerbates Murine Inflammatory Bowel Disease by Transcriptional Activation of Matrix Metalloproteinase 12
by Shih-Yao Chen, Chuan-Yin Fang, Bing-Hwa Su, Hao-Ming Chen, Shih-Chi Huang, Po-Ting Wu, Ai-Li Shiau and Chao-Liang Wu
Biomedicines 2024, 12(4), 780; https://doi.org/10.3390/biomedicines12040780 - 2 Apr 2024
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Abstract
Inflammatory bowel disease (IBD) is an inflammatory condition affecting the colon and small intestine, with Crohn’s disease and ulcerative colitis being the major types. Individuals with long-term IBD are at an increased risk of developing colorectal cancer. Early growth response protein 1 (Egr1) [...] Read more.
Inflammatory bowel disease (IBD) is an inflammatory condition affecting the colon and small intestine, with Crohn’s disease and ulcerative colitis being the major types. Individuals with long-term IBD are at an increased risk of developing colorectal cancer. Early growth response protein 1 (Egr1) is a nuclear protein that functions as a transcriptional regulator. Egr1 is known to control the expression of numerous genes and play a role in cell growth, proliferation, and differentiation. While IBD has been associated with severe inflammation, the precise mechanisms underlying its pathogenesis remain unclear. This study aimed to investigate the role of Egr1 in the development of IBD. High levels of Egr1 expression were observed in a mouse model of colitis induced by dextran sulfate sodium (DSS), as determined by immunohistochemical (IHC) staining. Chronic DSS treatment showed that Egr1 knockout (KO) mice exhibited resistance to the development of IBD, as determined by changes in their body weight and disease scores. Additionally, enzyme-linked immunosorbent assay (ELISA) and IHC staining demonstrated decreased expression levels of proinflammatory cytokines such as IL-1β, IL-6, and TNF-α, as well as matrix metalloproteinase 12 (MMP12). Putative Egr1 binding sites were identified within the MMP12 promoter region. Through reporter assays and chromatin immunoprecipitation (ChIP) analysis, it was shown that Egr1 binds to the MMP12 promoter and regulates MMP12 expression. In conclusion, we found that Egr1 plays a role in the inflammation process of IBD through transcriptionally activating MMP12. Full article
(This article belongs to the Special Issue MicroRNA and Its Role in Human Health)
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17 pages, 1466 KiB  
Article
Differential Expression of MicroRNA (MiR-27, MiR-145) among Dental Pulp Stem Cells (DPSCs) Following Neurogenic Differentiation Stimuli
by Charlton Bassett, Hunter Triplett, Keegan Lott, Katherine M. Howard and Karl Kingsley
Biomedicines 2023, 11(11), 3003; https://doi.org/10.3390/biomedicines11113003 - 9 Nov 2023
Cited by 1 | Viewed by 1133
Abstract
This study sought to evaluate the expression of previously identified microRNAs known to regulate neuronal differentiation in mesenchymal stem cells (MSCs), including miR-27, miR-125, miR-128, miR-135, miR-140, miR-145, miR-218 and miR-410, among dental pulp stem cells (DPSCs) under conditions demonstrated to induce neuronal [...] Read more.
This study sought to evaluate the expression of previously identified microRNAs known to regulate neuronal differentiation in mesenchymal stem cells (MSCs), including miR-27, miR-125, miR-128, miR-135, miR-140, miR-145, miR-218 and miR-410, among dental pulp stem cells (DPSCs) under conditions demonstrated to induce neuronal differentiation. Using an approved protocol, n = 12 DPSCs were identified from an existing biorepository and treated with basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF), which were previously demonstrated to induce neural differentiation markers including Sox1, Pax6 and NFM among these DPSCs. This study revealed that some microRNAs involved in the neuronal differentiation of MSCs were also differentially expressed among the DPSCs, including miR-27 and miR-145. In addition, this study also revealed that administration of bFGF and EGF was sufficient to modulate miR-27 and miR-145 expression in all of the stimulus-responsive DPSCs but not among all of the non-responsive DPSCs—suggesting that further investigation of the downstream targets of these microRNAs may be needed to fully evaluate and understand these observations. Full article
(This article belongs to the Special Issue MicroRNA and Its Role in Human Health)
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11 pages, 672 KiB  
Communication
MicroRNAs Associated with Disability Progression and Clinical Activity in Multiple Sclerosis Patients Treated with Glatiramer Acetate
by Ignacio Casanova, María I. Domínguez-Mozo, Laura De Torres, Yolanda Aladro-Benito, Ángel García-Martínez, Patricia Gómez, Sara Abellán, Esther De Antonio and Roberto Álvarez-Lafuente
Biomedicines 2023, 11(10), 2760; https://doi.org/10.3390/biomedicines11102760 - 12 Oct 2023
Cited by 2 | Viewed by 890
Abstract
MicroRNAs (miRNAs) are promising biomarkers in multiple sclerosis (MS). This study aims to investigate the association between a preselected list of miRNAs in serum with therapeutic response to Glatiramer Acetate (GA) and with the clinical evolution of a cohort of relapsing–remitting MS (RRMS) [...] Read more.
MicroRNAs (miRNAs) are promising biomarkers in multiple sclerosis (MS). This study aims to investigate the association between a preselected list of miRNAs in serum with therapeutic response to Glatiramer Acetate (GA) and with the clinical evolution of a cohort of relapsing–remitting MS (RRMS) patients. We conducted a longitudinal study for 5 years, with cut-off points at 2 and 5 years, including 26 RRMS patients treated with GA for at least 6 months. A total of 6 miRNAs from a previous study (miR-9.5p, miR-126.3p, mir-138.5p, miR-146a.5p, miR-200c.3p, and miR-223.3p) were selected for this analysis. Clinical relapse, MRI activity, confirmed disability progression (CDP), alone or in combination (No Evidence of Disease Activity-3) (NEDA-3), and Expanded Disability Status Scale (EDSS), were studied. After multivariate regression analysis, miR-9.5p was associated with EDSS progression at 2 years (β = 0.23; 95% CI: 0.04–0.46; p = 0.047). Besides this, mean miR-138.5p values were lower in those patients with NEDA-3 at 2 years (p = 0.033), and miR-146a.5p and miR-126.3p were higher in patients with CDP progression at 2 years (p = 0.044 and p = 0.05 respectively. These results reinforce the use of microRNAs as potential biomarkers in multiple sclerosis. We will need more studies to corroborate these data and to better understand the role of microRNAs in the pathophysiology of this disease. Full article
(This article belongs to the Special Issue MicroRNA and Its Role in Human Health)
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Review

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22 pages, 1660 KiB  
Review
Virus-Induced MicroRNA Modulation and Systemic Sclerosis Disease
by Irene Soffritti, Maria D’Accolti, Francesca Bini, Eleonora Mazziga, Dario Di Luca, Clara Maccari, Maria-Cristina Arcangeletti and Elisabetta Caselli
Biomedicines 2024, 12(6), 1360; https://doi.org/10.3390/biomedicines12061360 - 19 Jun 2024
Viewed by 238
Abstract
MicroRNAs (miRNAs) are short noncoding RNA sequences that regulate gene expression at the post-transcriptional level. They are involved in the regulation of multiple pathways, related to both physiological and pathological conditions, including autoimmune diseases, such as Systemic Sclerosis (SSc). Specifically, SSc is recognized [...] Read more.
MicroRNAs (miRNAs) are short noncoding RNA sequences that regulate gene expression at the post-transcriptional level. They are involved in the regulation of multiple pathways, related to both physiological and pathological conditions, including autoimmune diseases, such as Systemic Sclerosis (SSc). Specifically, SSc is recognized as a complex and multifactorial disease, characterized by vascular abnormalities, immune dysfunction, and progressive fibrosis, affecting skin and internal organs. Among predisposing environmental triggers, evidence supports the roles of oxidative stress, chemical agents, and viral infections, mostly related to those sustained by beta-herpesviruses such as HCMV and HHV-6. Dysregulated levels of miRNA expression have been found in SSc patients compared to healthy controls, at both the intra- and extracellular levels, providing a sort of miRNA signature of the SSc disease. Notably, HCMV/HHV-6 viral infections were shown to modulate the miRNA profile, often superposing that observed in SSc, potentially promoting pathological pathways associated with SSc development. This review summarizes the main data regarding miRNA alterations in SSc disease, highlighting their potential as prognostic or diagnostic markers for SSc disease, and the impact of the putative SSc etiological agents on miRNA modulation. Full article
(This article belongs to the Special Issue MicroRNA and Its Role in Human Health)
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17 pages, 1411 KiB  
Review
Impact of Long-Lasting Environmental Factors on Regulation Mediated by the miR-34 Family
by Peter Štefánik, Martina Morová and Iveta Herichová
Biomedicines 2024, 12(2), 424; https://doi.org/10.3390/biomedicines12020424 - 12 Feb 2024
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Abstract
The present review focuses on the interactions of newly emerging environmental factors with miRNA-mediated regulation. In particular, we draw attention to the effects of phthalates, electromagnetic fields (EMFs) and a disrupted light/dark cycle. miRNAs are small non-coding RNA molecules with a tremendous regulatory [...] Read more.
The present review focuses on the interactions of newly emerging environmental factors with miRNA-mediated regulation. In particular, we draw attention to the effects of phthalates, electromagnetic fields (EMFs) and a disrupted light/dark cycle. miRNAs are small non-coding RNA molecules with a tremendous regulatory impact, which is usually executed via gene expression inhibition. To address the capacity of environmental factors to influence miRNA-mediated regulation, the miR-34 family was selected for its well-described oncostatic and neuro-modulatory properties. The expression of miR-34 is in a tissue-dependent manner to some extent under the control of the circadian system. There is experimental evidence implicating that phthalates, EMFs and the circadian system interact with the miR-34 family, in both lines of its physiological functioning. The inhibition of miR-34 expression in response to phthalates, EMFs and light contamination has been described in cancer tissue and cell lines and was associated with a decline in oncostatic miR-34a signalling (decrease in p21 expression) and a promotion of tumorigenesis (increases in Noth1, cyclin D1 and cry1 expressions). The effects of miR-34 on neural functions have also been influenced by phthalates, EMFs and a disrupted light/dark cycle. Environmental factors shifted the effects of miR-34 from beneficial to the promotion of neurodegeneration and decreased cognition. Moreover, the apoptogenic capacity of miR-34 induced via phthalate administration in the testes has been shown to negatively influence germ cell proliferation. To conclude, as the oncostatic and positive neuromodulatory functions of the miR-34 family can be strongly influenced by environmental factors, their interactions should be taken into consideration in translational medicine. Full article
(This article belongs to the Special Issue MicroRNA and Its Role in Human Health)
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