Search Results (4,324)

Background: It is observed that there are a limited number of scientific studies investigating the effect of cocaine use disorder on microRNA (miRNA) levels in human peripheral blood. This study aimed to identify candidate miRNAs that may play a role in the regulation of cocaine addiction by detecting changes in the expression of some miRNAs (miR-9-5p, miR-26b-5p, miR-132-3p, and miR-134-5p) in the peripheral whole blood of cocaine addicts. Methods: Peripheral blood samples were collected from 12 Turkish male individuals with cocaine abuse, 11 Turkish male individuals undergoing treatment for cocaine abuse, and 16 healthy Turkish male individuals without any substance abuse. The change in the expression of microRNAs was determined by quantitative real-time polymerase chain reaction (RT-qPCR). In statistical analyses, ΔCt values were analyzed for the expression of miRNAs. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic adequacy of peripheral blood miRNAs. Results: miR-132-3p and miR-134-5p were downregulated in the addict group compared to the control group (p < 0.05). The areas under the curves (AUCs) of the ROC curve of miR-132-3p and miR-134-5p were significant at 0.778 and 0.744, respectively. Conclusions: This study suggests that miR-132-3p and miR-134-5p may have function as therapeutic markers in the treatment of cocaine use disorder. Full article

Background and Objectives: The clinical differentiation of peripheral involvement within the spondyloarthritis (SpA) spectrum remains a significant challenge. Identifying patients at the stage of psoriasis without clinical arthritis (PsO), before the onset of overt arthritis, is crucial for early disease management. MicroRNAs (miRNAs) have emerged as potential epigenetic regulators in inflammatory rheumatic diseases. This study aimed to identify circulating miRNA profiles that serve as discriminative biomarkers between PsO and peripheral SpA (p-SpA). Materials and Methods: This exploratory study was conducted in two phases. In the preliminary discovery phase, plasma miRNA expression was analyzed using high-throughput microarrays in patients with p-SpA (modeled by peripheral psoriatic arthritis, n = 6), PsO (psoriasis without clinical arthritis, n = 3), and osteoarthritis (n = 3). In the validation phase, candidate miRNAs were verified using TaqMan-based qPCR in an independent cohort (n = 30) of various SpA phenotypes, categorized into those with peripheral arthritis (SpA-A) and those without (SpA-N). Results: The preliminary discovery phase identified altered levels of hsa-miR-140-5p, hsa-miR-192-5p, and hsa-miR-146a-5p among the groups; however, due to the small sample size, these initial findings required strict downstream verification. Functional enrichment analysis revealed that these candidate miRNAs primarily targeted the NF-κB signaling pathway (hsa04064) and Toll-like receptor (TLR) signaling pathway (hsa04620). The validation cohort confirmed that these three miRNAs could reliably differentiate SpA-A from SpA-N patients. Furthermore, bioinformatic mapping predicted that downstream targets, including TRAF6, IRAK1, and CXCL2, may be associated with these clinical phenotypes, serving as hypothesis-generating observations for future studies. Conclusions: Our findings suggest that specific plasma miRNA profiles are associated with the inflammatory pathways driving peripheral involvement in the SpA spectrum. These miRNAs represent potential biomarkers associated with peripheral arthritis in the SpA spectrum. While they offer new molecular insights into disease pathogenesis, their predictive value for identifying PsO patients at risk of developing overt arthritis requires confirmation in future longitudinal studies. Full article

Cancer is one of the leading causes of mortality and morbidity worldwide. Various studies have highlighted the involvement of microRNAs (miRNAs) in tumor initiation and progression. MiRNAs are endogenous, non-coding, single-stranded RNA molecules that interact with the 3′-untranslated region (3′-UTR) of target mRNAs to inhibit mRNA translation or promote mRNA degradation. Various studies have reported that MIR133A is expressed at reduced levels in many tumor tissues and inhibits tumor progression. In this review, we comprehensively summarize the interactions of MIR133A and its target genes in the most commonly diagnosed cancers, namely, breast, lung, colorectal, gastric, and prostate. These results demonstrated that MIR133A is one of the optimal biomarkers for the diagnosis, prognosis, and prediction of various tumors, providing insights into the clinical management and practice of malignant tumors. Full article

Excessive tail fat deposition in sheep limits feed conversion efficiency and carcass quality, making the genetic improvement of this trait a priority. This study aimed to elucidate the molecular mechanisms regulating ovine fat metabolism. We analyzed the tissue specific expression of two candidate microRNAs, miR-320d and miR-151b, alongside their target genes SCD and ACACA, across tissues from fat-tailed and thin-tailed sheep using quantitative real-time PCR. The regulatory function of the tail fat specific miR-320d was further validated in vitro using isolated ovine tail preadipocytes. Results indicated that miR-320d and miR-151b are specifically highly expressed in tail and subcutaneous adipose tissues, respectively, and correlate negatively with their target genes. Dual-luciferase reporter assays confirmed that miR-320d directly targets the 3′UTR of SCD and suppresses its transcription. Overexpression of miR-320d significantly inhibited the proliferation of tail preadipocytes and downregulated downstream genes in the fatty acid metabolism pathway, including ACACA, ELOVL6, ELOVL5, and FASN. In conclusion, miR-320d exerts a negative regulatory effect on sheep tail fat deposition by suppressing preadipocyte proliferation and fatty acid synthesis, while miR-151b emerges as a potential candidate for subcutaneous fat regulation. Full article

Lichen sclerosus (LS) is a chronic inflammatory skin disorder with an incompletely understood molecular pathogenesis. This systematic review aimed to synthesize current evidence on key molecular mechanisms underlying the disease, with a particular focus on immune dysregulation, epigenetic modifications, and tissue remodeling. A structured literature search identified studies employing transcriptomic, epigenetic, and experimental approaches. The strongest evidence consistently supports a central role of immune activation, particularly T cell-mediated responses involving Th1- and Th17-related pathways, accompanied by increased expression of pro-inflammatory cytokines and activation of the NF-κB signaling pathway. Epigenetic and post-transcriptional mechanisms, including dysregulated microRNAs (notably miR-155-5p) and altered DNA methylation patterns, may sustain immune imbalance and fibroblast activation partly via modulation of the FOXO signaling pathway. In parallel, experimental and multi-omics studies highlight enhanced fibroblast activity and extracellular matrix remodeling, largely associated with the TGF-β signaling pathway, linking inflammation with progressive fibrosis. Emerging data also suggest interactions between immune signaling and metabolic alterations, although these findings remain preliminary. Overall, the available evidence indicates that LS may involve a complex interplay between immune, epigenetic, and fibrotic mechanisms. While several molecular pathways and candidate biomarkers have been identified, their clinical relevance requires further validation in larger, well-designed studies. Full article

Laccases (EC 1.10.3.2, LAC) are copper-containing glycoproteins involved in lignin biosynthesis, and as such, they play important roles in plant development and stress responses. In this study, a genome-wide analysis of the LAC gene family was performed in Pinus massoniana (Chinese red pine), identifying 78 PmaLAC genes, all predicted to encode cell membrane-localized proteins. These genes were unevenly distributed across eight chromosomes, with notable clusters on chromosomes 7 and 8, indicating gene duplication-driven expansion in P. massoniana. Phylogenetic analysis revealed that PmaLAC genes are classified into five subfamilies, reflecting the lineage-specific expansion and evolutionary divergence of gymnosperm LAC genes. Conserved motif and gene structure analyses showed high conservation among PmaLAC proteins. Promoter analysis identified numerous cis-acting elements related to hormone signaling, stress, and light responses. RNA-seq analysis revealed distinct tissue-specific expression patterns for PmaLAC gene family members. Moreover, degradome analysis combined with dual-luciferase assays supported the interaction between miR397c-9 and PmaLAC31, suggesting that miR397c-9 negatively regulates PmaLAC31 and indicating a potentially conserved miRNA-mediated regulatory mechanism. Overall, this study provides a systematic overview of the composition, evolution, and potential regulation mechanisms of the PmaLAC gene family in P. massoniana, providing a useful resource for future functional characterization of PmaLAC genes. Full article

Background: Designing studies to increase knowledge of the beneficial effects of volatile halogenated anaesthetics(VHAs) is critical to understand the mechanisms activated by myocardial conditioning during ischaemia-reperfusion(I/R) injury. Our research group has identified specific enzymes associated with the SAFE/RISK signalling pathways involved in halogen-induced cardioprotection and has observed a direct correlation between the expression of specific microRNA(miRNAs) and the cardioprotective effect conferred by VHA. Objective: This protocol study has been designed to increase knowledge regarding the cardioprotective effects generated by induced cardioprotective miRNAs after exposure to halogenated drugs without subjecting the patient to additional surgical procedures. Methods: The experimental design that is proposed will be performed with isogenic Wistar rats, all subjected to an I/R procedure. The animals will be randomly divided into two groups: the Donor group and the Recipient group. Half of the rats included in both groups will be exposed to sevoflurane (S), a hypnotic drug, during the I/R procedure, and the other half will be injected with propofol (P), a hypnotic. EVs will be isolated from plasma samples extracted from rats in the Donor group 24 h after the I/R procedure. In vitro EV characterisation will be performed by conducting an ultramorphological analysis, identifying the EV immunophenotype, and quantifying miRNAs. Cardiac function will be assessed by transthoracic echocardiography, histological, and immunohistochemical analyses. Results: The results derived from studies conducted according to this experimental design will support its validation as a preclinical study by regulatory authorities for approval and will serve to design a Phase I clinical trial. Conclusions: The proposed scientific rationale of applying this proposed experimental design will enable the generation of knowledge ‘from the bench to the bedside’ regarding miRNAs with cardioprotective properties induced by exposure to halogenated agents, which could be considered as biomarkers of cardioprotection. Furthermore, biomarker administration could reduce cardiac damage in patients undergoing additional cardiac surgery. Full article

Emerging evidence shows long non-coding RNAs (lncRNAs) as critical regulators of osteoarthritis (OA) progression, often acting in complex networks with microRNAs (miRNAs). In our study, we investigated the potential regulatory function of the lncRNA MEG3/miR-21-5p axis in the OA phenotype of chondrocytes. Differential gene expression analysis in damaged vs. intact cartilage was performed, re-analyzing existing public RNA-seq data. MiRTarBase, LncRNADisease, and Open Targets databases were utilized to identify miR-21-5p target genes and OA-associated lncRNAs and genes. Functional enrichment analysis and protein–protein interaction (PPI) network construction were performed using the DAVID and STRING databases, respectively. MEG3, miR-21-5p, SOX5, COL2A1 and ACAN mRNA expressions were assessed by qRT-PCR. The role of the MEG3/miR-21-5p axis in OA chondrocytes was examined using transfection experiments. Eighty-one lncRNAs displayed significant differences in expression between damaged and intact cartilage, including MEG3. Bioinformatic analysis indicated that MEG3 interacts with miR-21-5p, while SOX5 was identified to be a putative target of miR-21-5p. MEG3 and SOX5 expression levels were significantly downregulated in OA chondrocytes, whereas miR-21-5p expression was upregulated. Silencing of MEG3 resulted in increased miR-21-5p levels in chondrocytes. Conversely, inhibition of miR-21-5p led to increased SOX5 expression and anabolic markers COL2A1 and ACAN. Notably, MEG3 silencing significantly reduced SOX5 expression, an effect that was reversed upon miR-21-5p inhibition. Our findings highlight a potential regulatory role of the dysregulated MEG3/miR-21-5p axis in modulating the anabolic phenotype of chondrocytes through regulation of SOX5 expression. This novel lncRNA/miRNA/mRNA regulatory network may represent a candidate therapeutic axis for knee osteoarthritis. Full article

Host microRNAs (miRNAs) are widely proposed as innate antiviral effectors against SARS-CoV-2, yet whether they actually restrict infection in lung epithelial cells remains unresolved. Two of the most-cited candidates, miR-29a-3p and miR-15b-5p, are predicted to bind both the viral genome and key entry/trafficking factors such as Furin and ATG9A, but functional evidence is fragmented and often contradictory. Here, we put both miRNAs to the test in human Calu-3 cells infected with the SARS-CoV-2 Beta and Omicron BA.1 variants, using parallel gain- and loss-of-function strategies coupled to RT-qPCR of viral and cellular transcripts and back-titration of infectious progeny on VeroE6/TMPRSS2 cells. Both miRNAs transiently suppressed viral gene expression at 6 hpi, but this early dampening was followed by a marked transcript rebound at 24 hpi, especially for Omicron, with virtually no impact on total extracellular viral RNA. More strikingly, miR-15b modulation enhanced infectious virus output during Beta infection, and miR-29a overexpression boosted Omicron BA.1 infectivity, while Furin, ATG9A, AKT3, and TFEB showed only modest, condition-dependent shifts. Rather than acting as clean antiviral effectors, miR-29a and miR-15b emerge as context-dependent modulators that can paradoxically favor SARS-CoV-2 replication—a cautionary signal for miRNA-based antiviral strategies. Full article

Objective: Lung cancer (LC) remains a leading cause of cancer mortality worldwide. Thymoquinone (TQ), a bioactive compound derived from Nigella sativa, possesses anti-inflammatory and antioxidant properties, but its precise mechanisms concerning miRNA regulation in LC are poorly defined. This study investigates the anti-cancer potential of TQ through modulation of microRNA signaling in LC. Methods: We employed an integrated approach combining bioinformatic predictions with rigorous experimental validation in A549 lung adenocarcinoma cells and SHP-77 human small-cell lung carcinoma (SCLC) cells. Bioinformatic analyses predicted miRNA targets, and experimental techniques included dual-luciferase reporter assays, miRNA inhibition, TaqMan RT-qPCR, cell-based ELISA, and Western blotting to dissect the molecular pathway. Results: We identified the transcription factor BACH1 as a direct and novel target of hsa-miR-155-5p. TQ potently suppressed interferon-γ-induced expression of both hsa-miR-155-5p and its target, BACH1. This TQ-mediated suppression led to subsequent downregulation of the key metastasis-promoter Matrix Metalloproteinase-9 (MMP-9). Genetic inhibition of miR-155-5p or direct BACH1 inhibition phenocopied the effects of TQ, confirming the functional significance of this axis. Thus, we define a novel oncogenic signaling cascade—the hsa-miR-155-5p/BACH1/MMP-9 axis that is effectively disrupted by TQ. Conclusions: This represents the first evidence that TQ exerts its anti-cancer effects in LC through the modulation of the critical signaling cascade (hsa-miR-155-5p → BACH1 → MMP-9). Our findings establish TQ as a multi-targeted agent capable of simultaneously inhibiting miRNA-mediated oncogenic signaling and protein-level effectors. The dual therapeutic action of TQ represents a novel therapeutic strategy and underscores its potential for synergistic combination therapies. Full article

MicroRNAs are important regulators of skeletal muscle development and regeneration; however, the molecular basis by which exercise-induced miRNAs preserve middle-aged muscle function remains to be elucidated. This study aimed to investigate how aerobic exercise delays skeletal muscle attenuation by reversing age-related miRNAs dysregulation in male mice. Twelve-month-old male C57BL/6J mice (MC) (n = 8/group) were randomly assigned to a sedentary control group (OC) or an aerobic exercise group (OE) (12 m/min, 40 min/session, three sessions/week, for 12 weeks). miRNA sequencing identified differentially expressed miRNAs (DEmiRNAs), followed by miRNA–mRNA network construction. The results demonstrated that aerobic exercise improved muscle strength and mass while attenuating early atrophy and fibrosis. Four atrophy-associated DEmiRNAs (miR-150-5p, miR-199a-5p, miR-3535, and miR-329-5p) were reversed after aerobic exercise intervention. GO and KEGG profiling demonstrated that target genes were predominantly involved in protein binding and the Wnt signaling pathway. miR-199a-5p and miR-150-5p, with the most predicted targets, were selected as candidate mechanistic contributors, and FZD4 was confirmed as a common downstream target. Further analysis confirmed that miR-199a-5p and miR-150-5p inhibition attenuated D-galactose-induced C2C12 myotube atrophy, reducing Atrogin-1 and increasing MyoD1, FZD4, and β-catenin expression. These findings suggest that the exercise-induced miR-150-5p/miR-199a-5p axis may alleviate muscle aging in middle age via the restoration of key proteins in Wnt signaling and contribute preliminary observational evidence relevant to the understanding of aerobic exercise intervention in sarcopenia. Full article

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

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

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

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