Search Results (3,472)

Objective: Diabetic kidney disease (DKD) is characterized by podocyte injury and impaired autophagy. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) exhibit therapeutic potential for DKD, yet their mechanisms remain unclear. This study investigated whether BMSC-Exos restore podocyte autophagy via the miR-143-3p/Bcl-2/Beclin1 axis to delay DKD progression. Methods: A high-glucose (HG)-induced podocyte injury model was established using mouse podocytes (MPC5). Autophagy-related proteins (Beclin1, Bcl-2, LC3) and the injury marker desmin were analyzed by Western blot and immunofluorescence (IF). High-throughput sequencing identified BMSC-Exos-enriched miRNAs, with the miR-143-3p/Bcl-2 targeting relationship validated by dual-luciferase reporter assays. BMSCs transfected with miR-143-3p mimic or inhibitor were used to assess exosomes effects on autophagy and podocin expression. In vivo, DKD mice received tail vein injections of modified BMSC-Exos, followed by evaluation of physiological parameters, biochemical indices, and renal histopathology. Results: BMSC-Exos were successfully isolated and characterized. Fluorescence microscopy confirmed exosomes internalization by HG-treated MPC5 cells. BMSC-Exos upregulated Beclin1 and LC3-II while downregulating Bcl-2 and desmin, indicating enhanced autophagy. High-throughput sequencing revealed miR-143-3p enrichment in BMSC-Exos, and Bcl-2 was confirmed as a direct target of miR-143-3p. Exosomes from miR-143-3p mimic-transfected BMSCs further promoted autophagy and podocin expression. In DKD mice, BMSC-Exos reduced blood glucose, urinary albumin-to-creatinine ratio (UACR), and ameliorated renal damage, whereas miR-143-3p inhibition attenuated these effects. Conclusions: BMSC-Exos deliver miR-143-3p to target Bcl-2, thereby activating Beclin1-mediated autophagy and ameliorating DKD. This study elucidates a novel autophagy regulatory mechanism supporting BMSC-Exos as a cell-free therapy for DKD. Full article

MicroRNAs (miRNAs) are small non-coding RNA molecules approximately 20–22 nucleotides in length that regulate gene expression at the post-transcriptional level. By binding to target messenger RNAs (mRNAs), miRNAs inhibit translation or induce degradation, thus influencing a wide array of biological processes including development, inflammation, apoptosis, and tissue remodeling. Owing to their remarkable stability and tissue specificity, miRNAs have emerged as promising biomarkers in both clinical and forensic settings. In recent years, increasing evidence has demonstrated their utility in cardiovascular diseases, where they may serve as diagnostic, prognostic, and therapeutic tools. This systematic review aims to comprehensively summarize the role of miRNAs in cardiovascular pathology, focusing on their diagnostic potential in myocardial infarction, sudden cardiac death (SCD), and cardiomyopathies, and their applicability in post-mortem investigations. Following PRISMA guidelines, we screened PubMed, Scopus, and Web of Science databases for studies up to December 2024. The results highlight several miRNAs—including miR-1, miR-133a, miR-208b, miR-499a, and miR-486-5p—as robust markers for ischemic injury and sudden death, even in degraded or formalin-fixed autopsy samples. The high stability of miRNAs under extreme post-mortem conditions reinforces their potential as molecular tools in forensic pathology. Nevertheless, methodological heterogeneity and limited standardization currently hinder their routine application. Future studies should aim to harmonize analytical protocols and validate diagnostic thresholds across larger, well-characterized cohorts to fully exploit miRNAs as reliable molecular biomarkers in both clinical cardiology and forensic medicine. Full article

Retinitis pigmentosa (RP), an inherited retinal disorder, leads to progressive photoreceptor degeneration and irreversible blindness, with limited treatment options available. Emerging evidence implicates microRNAs (miRNAs) in the pathogenesis of retinal disease, yet understanding of their specific roles in RP remains incomplete. In this study, we employed high-throughput RNA sequencing to profile miRNA expression in a rd1 RP mouse model at postnatal day 14. Our analysis revealed 40 upregulated and 27 downregulated miRNAs in rd1 retinas compared to controls. Notably, miR-142a-5p, miR-223-3p, and miR-653-5p were significantly elevated, while miR-25-3p was downregulated. Given miR-142a-5p’s established roles in apoptosis and inflammation, we investigated its contribution to retinal degeneration. Knockdown of miR-142a-5p in rd1 mice improved retinal function and preserved outer nuclear layer thickness, suggesting a protective effect against photoreceptor loss. These findings highlight miR-142a-5p as a key regulator of RP progression and a promising therapeutic target for mitigating vision loss in retinal degenerative diseases. Full article

Background/Objectives: Premalignant laryngeal lesions carry a variable risk of malignant transformation to squamous cell carcinoma. Identifying reliable biomarkers that predict malignant transformation could improve patient management and surveillance strategies. The objective of this work is to perform a systematic review of the literature on biomarkers that predict malignant transformation of premalignant laryngeal lesions. Methods: We conducted a systematic review following PRISMA 2020 guidelines. The PubMed, Scopus and Embase databases, and Google Scholar were searched for studies published between January 2011 and November 2025. Studies investigating biomarkers that predict malignant transformation of histopathologically confirmed premalignant laryngeal lesions were included. Risk of bias was assessed using the ROBINS-I tool. Results: From 166 initially identified records, 11 studies met the inclusion criteria, including 730 patients. These studies investigated diverse biomarker categories such as protein markers (cortactin, FAK, NANOG, SOX2, CSPG4), immune markers (tumor-infiltrating lymphocytes, immune gene signatures), microRNAs (miR-183-5p, miR-155-5p, miR-106b-3p), and genetic markers (chromosomal instability, PIK3CA amplification and mutations, FGFR3 mutations). Five studies provided adequate follow-up data on transformation outcomes. Most studies showed a moderate to serious risk of bias primarily due to limited confounder control and incomplete reporting. Conclusions: While several promising biomarker candidates have been identified, the evidence base remains limited due to small sample sizes, heterogeneous methodologies, and inadequate follow-up data. Cortactin/FAK protein expression and immune signatures are the most promising but require validation in larger, well-designed prospective cohorts. Full article

MicroRNAs (miRNAs) play important roles in the regulation of melanogenesis and coat color in mammals. Short tandem target mimics (STTMs) have been used to block the functions of small RNA in animals and plants. To investigate the role of miR-5110 in melanogenesis, STTM was used to block the expression of miR-5110 (STTM-miR-5110). Luciferase reporter assay data indicated the miR-5110 regulates SOX10 expression by targeting its 3′-UTR. Overexpression of STTM-miR-5110 in alpaca melanocytes downregulated the expression of miR-5110 (decreased by about 38%, p < 0.05) and upregulated SOX10 mRNA (2.2-fold, p < 0.001) and protein (1.3-fold, p < 0.05) levels. Overexpression of STTM-miR-5110 in alpaca melanocytes increased the mRNA expression of melanogenic genes, including microphthalmia transcription factor (2.0-fold, p < 0.01), tyrosinase (1.6-fold, p < 0.01), tyrosinase-related protein 1 (approximately 3.9-fold, p < 0.001) and tyrosinase-related protein 2 (1.9-fold, p < 0.01). Overexpression of STTM-miR-5110 in alpaca melanocytes increased the protein expression of melanogenic genes, including microphthalmia transcription factor (1.9-fold, p < 0.05), tyrosinase (1.3-fold, p < 0.05), tyrosinase-related protein 1 (1.8-fold, p < 0.001) and tyrosinase-related protein 2 (1.6-fold, p < 0.05). The overexpression of pGL0-STTM-miR-5110 in alpaca melanocytes increased melanin production by approximately 26% (p < 0.05), pheomelanin production by approximately 38% (p < 0.05) and eumelanin production by approximately 56% (p < 0.001). In addition, overexpression of STTM-miR-5110 in alpaca melanocytes increased the TYR activity by 37% (p < 0.01). We also identified melanin granules in alpaca melanocytes transfected with STTM-miR-5110 under Fontana-Masson staining. These results suggest that STTM-miR-5110 upregulates melanogenesis by effectively blocking miR-5110 expression. Full article

Background: This study systematically investigates the therapeutic effects of naringenin (NAR) and oleuropein (OLE) on prostate cancer through miR-155-5p regulation. Methods: Experimental studies conducted on MAT-LyLu prostate cancer cell lines revealed that the application of NAR (50 μM) and OLE (75 μM) significantly increased miR-155-5p expression by 2.89-fold and 1.74-fold, respectively (p < 0.05). Bioinformatics analyses have indicated that miR-155-5p interacts with critical oncogenic pathways such as KRAS, CDK2, NF-κB, and TGF-β/Smad2. Computational analyses have revealed that miR-155-5p interacts with 16 critical oncogenic targets, including KRAS and CDK2. Molecular docking studies showed that NAR binds to the Switch I/II region of KRAS with a binding energy of −8.2 kcal/mol, while OLE binds to the ATP-binding pocket of CDK2 with an affinity of −9.1 kcal/mol. Pharmacokinetic evaluations revealed that NAR indicated high oral bioavailability (93.763% HIA) and full compliance with Lipinski’s rules, while OLE required advanced formulation strategies due to its high polarity. Network pharmacology analyses have shown that NAR affects lysosomal functions and enzyme regulation, while OLE affects G protein-coupled receptors and oxidoreductase activity. Results: Results indicate that NAR and OLE exhibit antitumor effects through multiple mechanisms by increasing miR-155-5p expression and inhibiting critical oncogenic targets in prostate cancer. Conclusion: Findings suggest that the dietary intake of these natural compounds (citrus and olive products) should be considered in prostate cancer prevention strategies, shedding light on the epigenetic mechanisms of polyphenols in cancer treatment and contributing to the development of new therapeutic strategies. Full article

Epicardial adipose tissue (EAT) function may influence the heart, given its metabolic actions and proximity to the heart. We hypothesized that diabetes mellitus (DM) alters miRNA expression across adipose tissue types, and that modifications in EAT may have critical implications for cardiac physiology. To test this, we compared EAT and subcutaneous adipose tissue (SAT) miRNA profiles between patients with and without DM and across tissues within each disease group. Paired biopsies from patients with (n = 18) and without DM (n = 46) undergoing cardiac surgery were analyzed using miRNA profiling and bioinformatics. Among 680 miRNAs screened, 34 were uniquely expressed in EAT, confirming a distinct molecular signature in this fat depot. Notably, miR-155-5p was significantly elevated in EAT from patients with DM, indicating a localized metabolic effect. In SAT, miR-93-3p and miR-223-3p were upregulated in patients with DM and consistently higher than in EAT, regardless of DM status, indicating tissue-specific regulation. miR-324-5p was more expressed in SAT of patients in the NDM group, reflecting combined effects of tissue type and DM. These patterns remained consistent across cardiac disease stratifications. Pathway analysis revealed that miRNAs enriched in EAT target genes involved in cardiomyocyte growth and differentiation. Overall, the findings highlight the unique miRNA profile of epicardial fat and its altered response to DM, supporting its relevance in cardiac physiology. Full article

Despite antiretroviral therapy, HIV proteins, such as Tat, persist in tissues, driving chronic inflammation. Cervical inflammation in females not only accelerates HIV progression but also increases the risk of other STIs; hence, understanding the underlying factors/regulators is vital. However, Tat-induced cervical inflammation and its regulation are hitherto poorly understood, which we investigated using TZM-bl cells. Tat stimulation in these cervical epithelial cells significantly increased the expression of various inflammatory mediators, including cytokines (IL-1β, TNF-α, IL-6, IL-17a, GM-CSF), chemokines (MIP-1α, MIP-1β), adhesion molecules (ICAM-1, P-Selectin, E-Selectin), and ROS. Further upregulation of inflammatory mediators (NF-κB, IRAK-4) along with TLR7 was observed in Tat-stimulated cells. Interestingly, Tat stimulation decreased miR-204-5p expression in these cells, suggesting a role in regulating Tat-mediated inflammatory processes. Using a gain-of-function approach, we further observed that the overexpression of miR-204-5p reduced the expression of IL-1β, TNF-α, IL-6, MIP-1α, MIP-1β, ICAM-1, P-Selectin, and ROS in the Tat-stimulated TZM-bl cells, along with NF-κB, IRAK-1, and IRAK-4. Using Western blotting and luciferase assays, miR-204-5p was further shown to directly target NF-κB. Here, we report that HIV-1 Tat stimulation in cervical epithelial cells downregulates hsa-miR-204-5p, thereby activating the pro-inflammatory TLR7/NF-κB axis, highlighting its relevance to understanding mechanisms underlying cervical inflammation. Full article

Background: Ewing’s sarcoma (EwS) is a pediatric bone and soft tissue cancer driven by the oncogenic fusion protein EWS::FLI1. Currently, EwS lacks targeted therapies, necessitating the identification of novel regulatory mechanisms. While the role of microRNAs and long non-coding RNAs has been explored in EwS, the presence and functional significance of circular RNAs (circRNAs) in EwS is not reported. This is the first study to report the presence and role of oncogenic circRNA, circZNF609 in EwS tumor progression. Methods: Expression of circZNF609 was validated in 5 different EwS cell lines using qPCR. Cellular localization of circZNF609 was identified using circFISH. Functional assays for proliferation, migration and apoptosis were performed in wild type and circZNF609 knocked down (KD) cell lines to confirm its oncogenic role. The impact of circZNF609 on EWS::FLI1 protein levels was confirmed using western blots, immunofluorescence, and polysome fractionation. Mechanistic insights were gained utilizing bioinformatic, dual-luciferase reporter assays, rescue experiments, and microscopy to identify and validate the circRNA-miRNA-mRNA regulatory axis. Results: We report the first identification of circZNF609 in EwS, demonstrating that its expression is EWS::FLI1-dependent. Functional analysis reveals that circZNF609 promotes cell proliferation and metastasis while inhibiting apoptosis. Mechanistically, circZNF609 acts as a molecular sponge for miR-145-5p. By sequestering this miRNA, circZNF609 prevents the translational repression of EWS::FLI1, thereby sustaining oncogenic signaling. Conclusions: These findings identify circZNF609 as a novel post-transcriptional regulator of EWS::FLI1 and establish its critical role in EwS pathogenesis. Our results suggest that targeting the circZNF609/miR-145-5p/EWS::FLI1 axis may offer a promising therapeutic strategy for EwS. Full article

Intervertebral disc (IVD) herniation is a complex and multifactorial condition with a challenging diagnosis and limited therapeutic options, highlighting the need for reliable biomarkers to improve clinical decision-making. The aim of this study was to identify circulating prognostic biomarkers of IVD herniation regression. The plasma proteomic profile and the expression of circulating non-coding RNAs were analysed in a rat model of IVD herniation and were correlated with herniation size. Four candidate proteins (TNC, COPS3, JUP, and GNAI2) were significantly correlated with herniation size, with TNC further validated by ELISA. Additionally, miR-143-3p, miR-10b-5p, miR-27a-3p, miR-140-5p, miR-155-5p, miR-146a-5p, and miR-21-5p were positively correlated with herniation size. Moreover, TNC, COPS3, JUP, and GNAI2 were found to be potential targets of miR-155-5p. This study provides the first combined proteomic and miRNA account of preclinical plasma biomarkers of IVD herniation size, where TNC-miR-155-5p emerge as promising elements of a regulatory module with IVD herniation prognostic potential. Full article

Seasonal biomass-burning haze in Northern Thailand produces sharp fluctuations in ambient fine particulate matter (PM), posing heightened health risks, particularly for individuals with diabetes mellitus (DM). To identify PM-responsive biomarkers and assess whether metabolic status modifies these responses, we first performed small RNA sequencing in a discovery cohort using plasma samples collected during low- and high-PM periods. Thirteen circulating microRNAs (miRNAs) were differentially expressed, including reduced miR-542-3p and elevated miR-29a-3p, novelmiR-203, and novelmiR-754, with predicted targets enriched in immune and endoplasmic-reticulum stress pathways. These four miRNAs were quantified by RT-qPCR in a longitudinal cohort of adults with (n = 28) and without DM (n = 29) sampled at three PM-defined timepoints across one full haze cycle. In non-DM individuals, miR-542-3p decreased at peak exposure while miR-29a-3p and novelmiR-203 increased, with values returning toward baseline at re-exposure. DM participants showed altered baseline levels and attenuated or reversed seasonal changes. Plasma IL-8 rose markedly at peak PM in both groups, mirroring exosome concentration increases measured by NTA, indicating a transient systemic inflammatory response. In an independent clinical cohort, only miR-542-3p differed significantly between lung-cancer patients and healthy controls. These findings indicate that PM exposure reconfigures circulating miRNA, exosomal, and cytokine profiles, and that DM modifies these responses, highlighting miR-542-3p and miR-29a-3p as environmentally responsive and disease-relevant biomarker candidates. Full article

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron degeneration with limited treatment options. In this study, we investigated the pathological role of microRNA-485-3p (miR-485-3p) in ALS, particularly its regulation of PGC-1α, a transcriptional coactivator essential for mitochondrial function and neuroprotection. We also evaluated the therapeutic potential of BMD-001S, a nanoparticle-based formulation encapsulating an antisense oligonucleotide targeting miR-485-3p. Our results demonstrated that miR-485-3p expression was significantly elevated in both SOD1^G93A-expressing HMC3 microglial cells and in the spinal cords of SOD1^G93A transgenic mice at late disease stages, implicating its contribution to ALS pathogenesis. Intravenous administration of BMD-001S effectively reduced miR-485-3p levels and restored PGC-1α mRNA and PGC-1α protein expression in the spinal cord. These molecular changes were associated with notable therapeutic outcomes, including reduced SOD1 protein aggregation, decreased neuroinflammation, and lower neurofilament light chain concentrations in cerebrospinal fluid. Moreover, BMD-001S treatment was associated with improvements in electrophysiological parameters and preservation of neuromuscular junction integrity during the observation period in SOD1^G93A transgenic mice. Taken together, these findings suggest that miR-485-3p/PGC-1α pathway is a promising therapeutic target in ALS and support the potential of BMD-001S as a novel treatment strategy for the disease. Full article

Diffuse large B-cell lymphoma (DLBCL) is the most common and clinically aggressive subtype of non-Hodgkin lymphoma (NHL). While novel therapies such as rituximab and polatuzumab vedotin have led to improved outcomes, approximately 35% of patients eventually develop relapsed or refractory disease. MicroRNAs (miRNAs), a class of endogenous single-stranded RNAs approximately 22 nucleotides in length, play a pivotal role in the regulation of gene expression at the post-transcriptional level through interactions with complementary target RNAs and contribute significantly to the development, progression, and treatment response of DLBCL. Oncogenic miRNAs, such as miR-155, miR-21, and the miR-17–92 cluster, promote proliferation, survival, immune evasion, and therapy resistance by modulating pathways including PI3K/AKT, NF-κB, and MYC. Conversely, tumor-suppressive miRNAs such as miR-34a, miR-144, miR-181a, and miR-124-3p inhibit oncogene activity and enhance apoptosis, with their loss often associated with adverse outcomes. Among these, miR-155 and miR-21 are particularly well studied, playing central roles in both tumor progression and remodeling of the tumor microenvironment. This review summarizes current evidence on the biological and clinical relevance of miRNAs in DLBCL, emphasizing their diagnostic and prognostic potential. Full article

Low-molecular-weight polycyclic aromatic hydrocarbons (LMW-PAHs), such as the 400 μM mixture of phenanthrene and fluorene used in this study, are prevalent environmental pollutants. Induction of epithelial–mesenchymal transition (EMT) by LMW-PAHs promote cell invasion and migration and contribute to disease pathogenesis. Long non-coding RNAs (lncRNAs) regulate gene expression by acting as competing endogenous RNAs (ceRNAs) that sequester microRNAs (miRNAs), a mechanism important for modulating EMT. Previously, regulation of the PI3K/AKT pathway and EMT in A549 cells are shown to occur through the hsa_circ_0039929/miR-15b-3p_R-1/FGF2 axis. Here, the functional role of the related LINC01376/miR-15b-3p_R-1/FGF2 axis in LMW-PAH-induced EMT was examined in A549 and H1299 cells. The miR-15b-3p_R-1 was downregulated, whereas LINC01376 and FGF2 were upregulated following LMW-PAH exposure. LINC01376 overexpression enhanced EMT, migration, and invasion. Interactions between miR-15b-3p_R-1 and FGF2, as well as direct binding of LINC01376 to miR-15b-3p_R-1, were confirmed experimentally. The results indicate that, in LMW-PAH-treated cells, LINC01376 functions as a ceRNA to sponge miR-15b-3p_R-1, thereby elevating FGF2 expression and promoting EMT, migration, and invasion. Identification of the LINC01376/miR-15b-3p_R-1/FGF2 regulatory axis highlighted as a key mechanism in LMW-PAH-driven EMT and suggests its potential as a therapeutic target in PAH-related pathologies. Full article

Zinc (Zn) is a mineral micronutrient that is essential for plant growth and development. Soil Zn deficiency or excess severely impacts plant health and crop yields. MicroRNAs (miRNAs) play crucial roles in plant responses to abiotic stress, but their roles in Zn homeostasis in important crop bread wheat (Triticum aestivum L.) remain unknown. This study investigated miRNA expression profiles in wheat roots under different Zn supply conditions using high-throughput sequencing. Phenotypic and physiological analyses revealed that high Zn promoted wheat plant growth, while low and excess Zn resulted in wheat plant growth inhibition and oxidative stress. A total of 798 miRNAs (including 70 known and 728 novel miRNAs) were identified; among them, 10 known and 122 novel miRNAs were differentially expressed. Many key miRNAs, such as miR397-5p, miR398, 4D_25791, and 5A_27668, are up-regulated under low Zn but down-regulated under high Zn and excess Zn. Target gene prediction and enrichment analysis revealed that the regulated genes of these miRNAs focused on “zinc ion transmembrane transporter activity”, “divalent inorganic cation transmembrane transporter activity”, and “cellular detoxification” processes in the low Zn vs. CK group. However, “glutathione metabolism” and “ABC transporter” pathways were obviously enriched in high Zn vs. excess Zn conditions, implying their potential functions in alleviating the oxidative damage and Zn efflux caused by Zn toxicity. Together, this study identified key miRNAs that respond to both Zn deficiency and excess Zn in bread wheat, revealing distinct regulatory patterns of the target genes in different Zn supply conditions. These findings provide a new field and valuable candidate miRNAs for molecular breeding aimed at improving zinc’s utilization efficiency in wheat. Full article