Search Results (12,478)

The Hippo–Yorkie (Yki) signaling pathway is a conserved regulator of tissue growth, and its dysregulation leads to excessive growth and tumorigenesis. Although several microRNAs (miRNAs) have been implicated in Hippo pathway regulation, how they modulate Yki activity in vivo remains incompletely understood. Here, we identify miR-137 as a suppressor of Yki-driven overgrowth in a Drosophila model. A functional miRNA screen revealed that miR-137 overexpression markedly suppresses Yki-induced eye overgrowth, whereas inhibition of miR-137 enhances eye overgrowth phenotypes. Through bioinformatic prediction and genetic screening, we identified Drep1 as a candidate downstream factor associated with miR-137 function. RNAi-mediated depletion of Drep1 phenocopies the suppressive effects of miR-137, whereas Drep1 overexpression enhances Yki-driven tissue overgrowth and proliferation. Consistent with these phenotypes, miR-137 overexpression or Drep1 depletion reduces the expression of canonical Yki target genes, including Diap1 and Expanded, indicating decreased Yki transcriptional output. Importantly, Drep1 knockdown was associated with reduced Yki immunostaining in a complementary wing-disk context, suggesting a potential link between Drep1 and Yki-associated signaling. Consistent with this, miR-137 also reduced the expression of ICAD, the mammalian homolog of Drep1, providing preliminary evidence that miR-137 may regulate ICAD expression in mammalian cells. Together, these findings support a potential regulatory relationship between miR-137 and Drep1 that modulates Yki-driven eye overgrowth and reveal an additional layer of Hippo pathway regulation in vivo. Full article

Background/Objectives: Inflammatory and oxidative-stress-related processes contribute to post-myocardial infarction (MI) remodeling and may influence long-term cardiovascular outcomes. Recent findings have highlighted the potential role of non-coding RNAs in regulating these processes. LncRNA MALAT1 acts as a ceRNA that “sponges” miR-146a, reducing its ability to repress downstream targets such as COX-2. The aim of this study was to assess MALAT1 and miR-146a expression in PBMCs and plasma COX-2 in controls and patients six months post-MI. In addition, we investigated whether MALAT1 rs3200401 and miR-146a rs2910164 variants were associated with MI susceptibility, MALAT1 and miR-146a expression, plasma COX-2 levels, and left ventricle (LV) echocardiographic parameters. Methods: The study included 534 patients and 381 controls for genetic analyses, while expression analyses were performed in a subset of 89 patients and 39 controls. TaqMan™ assays were used for genotyping and for quantification of MALAT1 and miR-146a expression. Plasma COX-2 levels were measured using ELISA. Results: Compared to controls, patients had higher MALAT1 expression, whereas lower miR-146a expression was observed only in unadjusted analyses. Plasma COX-2 levels were higher in patients with advanced heart failure (NYHA III–IV) compared with NYHA I-II. The rs3200401 TT genotype was more frequent in patients, whereas rs2910164 genotype distributions were similar between groups. The rs3200401-rs2910164 TG allele combination was associated with increased MI risk. Conclusions: MALAT1 may serve as a potential long-term biomarker of post-MI molecular alterations, whereas the role of miR-146a requires further investigation in larger cohorts. The rs3200401 variant may represent a genetic marker associated with MI susceptibility and adverse LV remodeling. Further studies are needed for confirmation. Full article

The bidirectional differentiation potential of skeletal muscle satellite cells (SMSCs) enables them to differentiate into myofibers or intramuscular adipocytes, which affects meat quality in livestock. However, how insulin regulates ovine SMSC metabolism remains poorly understood. SMSCs were isolated from the longissimus dorsi muscle of 1-day-old Hu sheep, cultured, identified, and induced to differentiate with insulin. After induction, lipid droplet formation and the number of nuclei per cell were assessed, and samples were collected before adipogenic induction (No_AD) and after adipogenic induction (AD) for qPCR and whole-transcriptome sequencing. Immunofluorescence confirmed cells were positive for PAX7 and DESMIN. Bodipy, Oil Red O, and hematoxylin staining revealed lipid droplets and multinucleated cells. Sequencing and qPCR indicated that insulin promoted fatty acid uptake and utilization, inhibited adipogenic differentiation, and promoted myogenic differentiation. Integrated ceRNA analysis suggested that miR-2447-z and MSTRG.8123.1 may coordinate muscle development and lipid metabolism. In conclusion, under insulin induction, ovine SMSCs may undergo metabolic adaptation through the ceRNA network mediated by miR-2447-z and MSTRG.8123.1, exhibiting enhanced myogenesis, suppressed adipogenesis, and lipid droplet accumulation. These findings provide new insights into insulin-regulated SMSC metabolism, suggesting that leveraging the bidirectional differentiation potential of SMSCs to in-fluence muscle characteristics and fat deposition may be a feasible approach for im-proving meat production traits in sheep. Full article

Background: Human breast milk (HBM), as the initial food for humans, is quite essential for infant development and also for health throughout the lifespan. Exosomes are bioactive components in HBM, yet their nutritional role remains poorly recognized. Objectives: This study investigates how HBM exosomes change with lactation and their potential role in infant growth and development. Methods: HBM samples were obtained at 2 and 6 months postpartum from a well-established birth cohort. Purified exosomes were detected using transcriptomic, lipidomic, and proteomic approaches. Then, multi-omics data were analyzed to compare differentially expressed miRNAs, lipids, and proteins along with different lactation periods and their association with the infant growth process. Results: Compared with the 2-month postpartum group, the expression levels of miR-214-3p, miR-199a-5p, miR-126-3p, miR-127-5p, miR-144-3p, and miR-4787-5p were down-regulated in the 6-month postpartum group. In addition, 190 lipids and 269 proteins were up-regulated in the 6-month postpartum group, whereas 15 lipids and 244 proteins were down-regulated. Enrichment analysis revealed that the predicted target genes of differentially expressed miRNAs were primarily involved in cell communication and axon guidance. In parallel, the differentially expressed proteins were enriched in biosynthesis of unsaturated fatty acids and fatty acid metabolism pathway, implying a potential role in adipogenesis and neurodevelopment. Conclusions: This study reveals that the cargo contents of HBM exosomes change with the lactation period and may adapt to the needs of infant growth and development, particularly adipogenesis and neurodevelopment. HBM exosomes may play an important role in transferring genetic information from mothers to infants and be related to infants’ development. The underlying mechanisms warrant further investigation and validation. Full article

The multifaceted oncogenic role of teratocarcinoma-derived growth factor 1 (TDGF1) in colon cancer remains incompletely understood. Through integrative bioinformatic and functional analyses, we identified a novel competing endogenous RNA (ceRNA) axis wherein the long non-coding RNA OLMALINC directly sponges hsa-miR-3614-5p, leading to the derepression of TDGF1. This OLMALINC/miR-3614-5p/TDGF1 axis promoted colon cancer cell proliferation, migration, invasion, and anti-apoptosis in vitro, whereas TDGF1 knockdown significantly suppressed tumor growth in vivo. Mechanistically, TDGF1 co-activated oncogenic signaling via the Thr88-dependent Nodal/Smad2 cascade and the Glypican-1-mediated MAPK/AKT pathway. Beyond cell-autonomous effects, transcriptomic and single-cell analyses revealed that elevated TDGF1 correlates with an immunosuppressive microenvironment, characterized by reduced immune infiltration and altered LGALS9-CD44 malignant-T cell communication. Clinically, high TDGF1 expression in a tissue microarray cohort was significantly associated with advanced T stage, reduced expression of specific mismatch repair proteins (MLH1/PMS2), and poor overall survival. Collectively, this study delineates the OLMALINC/miR-3614-5p/TDGF1 regulatory circuit and establishes TDGF1 as a multifaceted driver of tumor progression, highlighting its potential as a prognostic biomarker and therapeutic target in colon cancer. Full article

p53, miR-34a, and SIRT-1 are involved in cellular stress responses, senescence, and inflammation—processes central to the pathophysiology of atrial fibrillation (AF). In this study, circulating TP53 and SIRT-1 serum miR-34a expression were determined in patients with and without AF, in order to assess their associations with AF. We also checked their potential diagnostic utility as systemic biomarkers associated with AF. The study included 189 adults, 94 AF+, 95 AF−. Clinical, anthropometric, and biochemical data were collected. Whole-blood TP53 and SIRT-1 mRNA expression and serum miR-34a expression were quantified by RT-qPCR. ROC analysis and Youden-derived odds ratios assessed exploratory diagnostic performance. AF patients had significantly higher expression of TP53 (0.0352 vs. 0.0253; p < 0.001) and miR-34a (0.0215 vs. 0.0099; p < 0.001), but significantly lower expression of SIRT-1 (0.0079 vs. 0.0145; p < 0.001). The level of SIRT-1 expression showed the highest discriminatory performance (exploratory AUC = 0.6987; p < 0.0001). TP53 expression levels exceeding 0.0295 were associated with nearly threefold higher odds of AF (OR = 2.92, 95% CI: 1.61–5.28, p = 0.0006), whereas the expression levels of SIRT-1 and miR-34a were not significantly associated with AF in cut-off analysis. In the AF group, a positive correlation was found between the expression of TP53 and SIRT-1 (Rho = 0.3609, p < 0.001); however, it was not consistent with a canonical model of miR-34a-mediated SIRT-1 suppression. In turn, the expression of miR-34a correlated positively with age and C-reactive protein level and negatively with estimated glomerular filtration rate (eGFR). The obtained results suggest that AF is associated with altered expression of circulating TP53, SIRT-1, and miR-34a. However, due to the fact that the expression levels were measured in peripheral compartments, and not in atrial tissue, the obtained results should not be interpreted as direct evidence of AF-related atrial remodeling. For these reasons, further investigations involving simultaneous measurements of the TP53/miR-34a/SIRT-1 regulatory axis, both in the circulating compartment and atrial tissue, should be performed. Full article

Arrhythmogenic cardiomyopathy (ACM/ARVC) is an inherited myocardial disease characterized by progressive fibro-fatty replacement, ventricular arrhythmias, and an increased risk of sudden cardiac death. In addition to mutations in desmosomal genes, growing evidence suggests that microRNAs (miRNAs) actively contribute to disease pathogenesis by regulating key processes such as fibrosis, cell adhesion, and cardiac remodeling. This systematic review analyzed the main miRNAs identified in studies of human cardiac tissue and animal models of ARVC. Materials and Methods: Studies based on human myocardial tissue analysis (including autopsy and biopsy samples) and animal models of arrhythmogenic cardiomyopathy were included, using RNA sequencing, small RNA sequencing, miRNA arrays, and RT-qPCR. Studies on circulating miRNAs and narrative reviews were excluded. miRNAs were analyzed in relation to their functional pathways and their role in disease pathogenesis. Results: The synthesis of studies on human and animal cardiac tissue reveals a consistent miRNA signature associated with arrhythmogenic cardiomyopathy. MiR-21-5p and miR-29b-3p are associated with fibrosis and extracellular matrix remodeling, whereas miR-133a-b and miR-130a are linked to cardiomyocyte integrity loss and desmosomal dysfunction. A second group of miRNAs, including miR-217-5p, miR-708-5p, and miR-135b, regulates key pathways such as Wnt/β-catenin and Hippo signaling, contributing to structural remodeling and loss of cellular identity. Furthermore, downregulation of miR-499-5p is associated with mitochondrial dysfunction and cellular vulnerability, while the miR-142-3p, miR-182-5p, and miR-183-5p clusters contribute to differential molecular signatures compared with other cardiomyopathies. Overall, miRNAs converge on three main pathogenic axes: myocardial fibrosis, desmosomal impairment, and remodeling of cellular signaling pathways. Conclusions: The available evidence indicates that arrhythmogenic cardiomyopathy is regulated by a coordinated network of miRNAs that actively drives myocardial damage progression. These miRNAs represent not only biomarkers but also functional mediators of disease, suggesting potential diagnostic and therapeutic applications based on tissue-specific molecular signatures, including in post-mortem settings. Full article

To characterize the distinct expression profiles of microRNAs (miRNAs) in serum and tissue and to delineate the heterogeneity of their regulatory mechanisms in early-stage ovarian cancer (EOC), thereby identifying candidate biomarkers for non-invasive early diagnosis. Differentially expressed miRNAs were identified by integrating publicly available datasets of EOC tissues and serum samples from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Core miRNAs were subsequently screened through integrated differential expression analysis, weighted gene co-expression network analysis (WGCNA), and feature importance ranking derived from optimized machine learning models. Protein–protein interaction (PPI) networks and functional enrichment analyses (GO and KEGG) were performed on predicted target genes to systematically compare the functional discrepancies between serum- and tissue-derived miRNAs. No overlapping core miRNAs were observed between the two compartments. Serum miRNAs exhibited an overall up-regulated trend, whereas tissue miRNAs were predominantly down-regulated. Although the regulatory pathways demonstrated significant heterogeneity, they ultimately converged on the cell cycle and the PI3K-Akt signaling pathway, indicating high functional homology. Furthermore, serum miRNAs are not merely passive leakage products from tissues; current evidence suggests they may be selectively packaged into exosomes to participate in tumor regulation. Despite divergent expression profiles, serum and tissue miRNAs share homologous regulatory functions in EOC. These findings suggest that serum miRNAs accurately reflect the core molecular status of tumor tissues, providing a robust molecular foundation for liquid biopsy-based early detection strategies. Full article

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is strongly associated with atrial structural remodeling driven by activated cardiac fibroblasts. Autophagy has been implicated in AF-related atrial remodeling; however, the non-coding RNA mechanisms that govern autophagic activation in atrial fibroblasts under rapid electrical stress remain poorly understood. Methods: Human cardiac fibroblasts from adult atria (HCF-aa) were subjected to rapid electrical stimulation (RES) at 0.5 V/cm and 10 Hz. Expression levels of exosomal metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), cytoplasmic miR-204-5p, and microtubule-associated protein light chain 3B (LC3B) were measured using quantitative real-time PCR and Western blot analyses. Luciferase reporter assays were performed to confirm direct molecular interactions. The functional roles of MALAT1 siRNA, miR-204-5p mimics/antagomirs, rapamycin, and 3-methyladenine (3-MA) on LC3B expression and autophagic activation were assessed by Western blot and immunofluorescence confocal microscopy for LC3B puncta formation. Results: RES significantly induced exosomal MALAT1 expression in a voltage- and time-dependent manner, peaking at 2 h post-stimulation, while cytoplasmic MALAT1 levels remained unchanged. Cytoplasmic miR-204-5p exhibited an initial transient rise followed by a significant decline at 2 h, inversely correlating with peak MALAT1 levels. LC3B mRNA and protein expression subsequently increased, peaking at 6 and 16 h, respectively. Luciferase reporter assays confirmed that miR-204-5p directly binds both the MALAT1 transcript and the 3′-UTR of LC3B mRNA. MALAT1 knockdown augmented miR-204-5p levels and suppressed LC3B expression, while miR-204-5p overexpression attenuated RES-induced LC3B upregulation and LC3B puncta accumulation. Conversely, miR-204-5p inhibition further enhanced autophagic activation, as evidenced by increased LC3B puncta density. Conclusions: In HCF-aa subjected to RES, MALAT1 functions intracellularly as a competing endogenous RNA to putatively sequester miR-204-5p, thereby de-repressing LC3B expression and promoting autophagic activation. Concurrent exosomal secretion of MALAT1 may additionally serve as a paracrine signal to neighboring cells, though this requires future conditioned-media transfer experiments to confirm. Full article

Iron overload disrupts cellular homeostasis and drives ferroptosis through dysregulated iron metabolism. Non-coding RNAs (ncRNAs) are considered as key regulators of various biological functions and targets for a new generation of RNA therapeutics and biomarkers. However, few studies have investigated the regulatory roles of ncRNAs, particularly competitive endogenous RNAs (ceRNAs) in iron overload. This study performed whole-transcriptome sequencing to characterize the ceRNA network in ferric ammonium citrate (FAC)-induced iron-overloaded HT-1080 fibrosarcoma cells. A total of 208 differentially expressed mRNAs, 83 lncRNAs, and 170 circRNAs (q < 0.05) were identified, with hierarchical clustering revealing distinct expression patterns between control and iron-treated groups. KEGG enrichment implicated vitamin B6 metabolism (q < 0.001) and lysine degradation (q < 0.001) as key disrupted pathways. ceRNA network was conducted and further demonstrated lncRNA/circRNA-mediated regulation of ferroptosis genes via shared miRNA response elements. Notably, LINC-PINT-232 was implicated in the regulation of both ferritin heavy chain (FTH) and sequestosome 1 (SQSTM1), two ferroptosis-associated mRNAs. FTH upregulation mitigates iron toxicity through ferroxidase activity, while SQSTM1 modulates lipid peroxidation in ferroptosis. These findings provide a preliminary transcriptomic landscape for hypothesis generation regarding ncRNA-mediated regulatory mechanisms in iron overload-induced ferroptosis and offer a computational foundation for future functional and therapeutic investigations. Full article

Background: Osteoporosis (OP) is a chronic disease characterized by decreased bone mass and altered microarchitecture, leading to bone fragility and fracture risk. To date, although carbohydrate-binding proteins Galectins 1 and 3 (Gal-1/Gal-3) have been implicated in bone metabolism, inflammation and aging, their levels and potential regulation by microRNAs (miRNAs) have not yet been investigated in OP. Methods: In this pilot study, 13 osteoporotic (OP) and 10 non-osteoporotic (NOP) patients, all undergoing hip or knee arthroplasty, were enrolled. Due to the unavailability of DXA measurements, OP classification was based on cortical bone ratio and distal femoral cortical index. Clinical parameters and blood samples were collected preoperatively, while bone biopsies were obtained intraoperatively. ELISA and qRT-PCR were used to quantify Gal-1, Gal-3, miR-22 and miR-21 in bones and sera. Correlations with clinical parameters were assessed. Results: Several OP biopsies exhibited a reduction in Gal-1 levels, whereas miR-22, Gal-3 and miR-21 were increased. Serum analysis revealed similar dysregulation patterns, with increased miR-21 and decreased Gal-1 and miR-22 levels in several OP patients. Conclusions: This pilot study suggests a putative association of Gal-1, Gal-3, and their previously reported related miRNAs with osteoporotic bone status, indicating their potential involvement in OP-related bone metabolism. Full article

Background/Objectives: Cervical cancer is mainly driven by persistent infection with high-risk human papillomaviruses (HPV), particularly HPV16 and HPV18. Despite advances in cytology, HPV-DNA testing and vaccination, challenges remain in the triage of HPV-positive individuals, prognostic stratification and prediction of treatment response. Non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs and circular RNAs, together with host genetic factors influencing ncRNA expression and emerging lncRNA-encoded peptides, are increasingly recognized as regulators of HPV-associated carcinogenesis. This review summarizes their biological and potential clinical relevance. Methods: A structured literature search was conducted in PubMed and Scopus. Eligible studies included experimental, clinical, observational, genomic and translational investigations on ncRNA dysregulation, circulating or exosomal ncRNAs, treatment-response signatures, host genetic variation and lncRNA-encoded peptides in HPV-associated cervical precancer and cancer. Results: HPV oncoproteins can reshape host ncRNA networks through transcriptional and epigenetic mechanisms. Several miRNAs, lncRNAs and circRNAs are involved in cell-cycle control, apoptosis, senescence, epithelial–mesenchymal transition, immune regulation, DNA repair and treatment resistance. Circulating, exosomal and urinary ncRNA signatures have shown diagnostic or prognostic potential in exploratory cohorts. Specific lncRNAs, including ENSG00000267838/lnc-LENG9-5 and lncRNA-EME1, have been associated with chemoradiotherapy response and radioresistance. The lncRNA-encoded peptide TUBORF represents a novel preclinical therapeutic candidate, while genetic variation may further modulate lncRNA function in HPV-related cervical cancer. Conclusions: ncRNAs are promising candidates for risk stratification, non-invasive diagnosis, treatment-response prediction and therapeutic development in HPV-associated cervical disease. However, evidence remains exploratory, requiring prospective multicentre validation and standardized workflows before clinical implementation. Full article

The biosynthesis of sex pheromones in lepidopteran pheromone glands is tightly regulated by pheromone biosynthesis-activating neuropeptide (PBAN) signaling; yet the contribution of non-coding RNA-mediated post-transcriptional regulation remains largely unclear. This study aimed to characterize temporal transcriptomic changes, candidate non-coding RNA-mediated regulatory associations, and temporal molecular dynamics underlying transcriptional remodeling after PBAN treatment in Ostrinia furnacalis. First, we performed comprehensive whole-transcriptome sequencing (WTS) on 18 biologically independent samples collected at six time points (0, 20, 40, 60, 90, and 120 min) after PBAN injection. Then, we systematically identified and quantified the dynamic expression patterns of differentially expressed (DE) mRNAs, miRNAs, lncRNAs, and circRNAs in response to PBAN stimulation. By integratively analyzing these multidimensional omics datasets and inferring sequence-based interaction relationships, we inferred a dynamic candidate competing endogenous RNA (ceRNA) like regulatory network. The candidate ceRNA network anchored four core node genes: the PBAN receptor (PBANR), the rate-limiting enzyme acetyl-CoA carboxylase (ACC), and the terminal biosynthetic enzymes desaturase (DES) and fatty acyl-CoA reductase (FAR). The qRT-PCR results further support the temporal expression pattern of key genes during the PBAN response, suggesting that this network can provide a valuable resource for further functional studies. Full article

Type 2 diabetes mellitus (T2DM) is a major driver of chronic kidney disease and cardiovascular morbidity worldwide. Extracellular vesicles (EVs), particularly exosomes, carry microRNAs (miRNAs) that reflect the pathophysiological state of their parent cells and represent promising non-invasive biomarkers. This review comprehensively examines the diagnostic and mechanistic roles of EV-derived miRNAs in diabetic nephropathy (DN) and cardiovascular diseases (CVDs) associated with T2DM. A PRISMA-guided literature search of PubMed, Scopus, Web of Science, and Embase identified 847 articles published between January 2020 and June 2026, of which 156 studies met the inclusion criteria. Several urinary exosomal miRNAs demonstrated significant diagnostic performance for DN, including miR-4534 (AUC = 0.786), miR-136-5p (sensitivity 72.2%, specificity 78.4%), and miR-142-3p. A meta-analysis of circulating miRNAs in diabetic kidney disease reported a pooled AUC of 0.79. In the cardiovascular setting, exosomal miR-155-5p (AUC = 0.901), miR-15a-3p (AUC = 0.874), and a four-miRNA panel (miR-433-3p/let-7b/miR-30-5p/miR-122-5p; AUC = 0.833) demonstrated strong diagnostic performance for ischemic heart disease and carotid atherosclerosis in T2DM. Mechanistically, key EV-associated miRNAs, including miR-21, miR-192, and the anti-fibrotic miR-29 family, participate in fibrosis, inflammation, oxidative stress, endothelial dysfunction, and cardiac remodeling pathways. EV-derived miRNAs therefore represent highly promising non-invasive biomarkers for the early diagnosis and monitoring of diabetic renal and cardiovascular complications. However, clinical translation requires standardized EV isolation and miRNA detection protocols, together with validation in large multicenter prospective cohorts. This review highlights the considerable diagnostic and translational potential of EV-derived miRNAs for precision medicine and liquid biopsy applications in T2DM complications. Full article

Prostate cancer (PrC) is one of the most common malignancies among men worldwide. However, the contribution of genetic variation in microRNA (miRNA) biogenesis pathway genes to PrC susceptibility remains poorly characterized in many ethnically diverse populations. We conducted a case–control study involving 532 PrC patients and 550 controls from the Volga-Ural region of Eurasia to evaluate the association of twenty-one single nucleotide polymorphisms (SNPs) with PrC risk using single-variant and polygenic approaches. Association analyses identified rs595055 in the AGO1 gene as significantly associated with PrC risk after correction for multiple testing. To evaluate the cumulative effect of genetic variation, weighted and unweighted polygenic risk scores (PRSs) were constructed. The weighted PRS was significantly associated with PrC risk (odds ratio per standard deviation increase = 1.63, 95% CI [1.43–1.85], P = 1.37 × 10⁻¹³), and demonstrated moderate discriminatory performance (AUC = 63.1%), outperforming the unweighted model. Individuals in the highest PRS quartile had approximately threefold higher odds of PrC than those in the lowest quartile. Combining the weighted PRS with prostate-specific antigen improved discrimination (AUC = 68.1%). These findings support the contribution of miRNA biogenesis pathway genes to PrC susceptibility and highlight the potential value of pathway-based polygenic risk stratification in understudied populations. Full article