Search Results (4,273)

Background and Objectives: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and have emerged as potential biomarkers in type 2 diabetes mellitus and its complications. This pilot exploratory study aimed to identify circulating miRNAs with differential expression in plasma from patients with newly diagnosed type 2 diabetes mellitus compared to age- and sex-matched healthy controls. Materials and Methods: Peripheral venous blood samples were collected from diabetic patients (n = 24) and controls (n = 12). Due to the exploratory nature of the study and limited sample material, samples were pooled within each group prior to plasma separation. Total RNA, including miRNAs, was extracted from plasma and analyzed using a high-throughput qPCR panel. Two normalization methods were applied to assess miRNA expression, and overlapping results were used for downstream analysis. Fold regulation was calculated using the 2^(−ΔCt) method. Results: A total of 33 and 42 miRNAs were identified as differentially expressed using the first and second normalization methods, respectively. Fourteen miRNAs were consistently downregulated across both methods. Several of these miRNAs, including hsa-miR-26a-5p, hsa-miR-146a-5p, hsa-miR-186-5p, hsa-miR-19a-3p, and hsa-miR-652-3p, have been previously associated with glucose metabolism, inflammation, and diabetic complications, such as retinopathy, neuropathy, and endothelial dysfunction. The pooling strategy enabled an efficient exploratory assessment of miRNA expression patterns while reducing inter-individual variability. Conclusions: This exploratory pilot study identifies a panel of circulating miRNAs with altered expression in pooled plasma samples from patients with newly diagnosed type 2 diabetes mellitus. These findings provide preliminary insights that warrant further validation in larger, individual-level studies to assess their diagnostic and prognostic potential. Full article

Background: Neuroinflammation is a key contributor to the progression of several neurodegenerative disorders, including Alzheimer’s disease, stroke, and small vessel disease. Emerging evidence highlights the role of circulating microRNAs (miRNAs) as non-invasive biomarkers of neuroinflammation and neuronal injury. miR-106a-5p, a member of the miR-17~92 cluster, is known to regulate inflammation, apoptosis, and vascular function. While typically studied in plasma or cerebrospinal fluid, gastric juice miRNAs represent a novel and underexplored source for biomarker discovery within the gut–brain axis. This exploratory study aimed to investigate the association between gastric juice miR-106a-5p expression and markers of neuroinflammation, including C-reactive protein (CRP), lactate dehydrogenase (LDH), and imaging-based evidence of neurodegeneration. Methods: A prospective, observational study was conducted on 38 participants (22 with neurodegenerative pathology and 16 healthy controls). Gastric juice samples were analyzed for miR-106a-5p using RT-qPCR, normalized to U6 snRNA. ΔCt values were used to determine relative expression. Statistical analyses included t-tests/Wilcoxon tests, ROC curve analysis, and correlation testing, with significance set at p < 0.05. Results: Patients with neurodegenerative changes exhibited significantly lower gastric miR-106a-5p expression compared to controls (p = 0.044). Elevated CRP and LDH levels were associated with higher ΔCt values (indicating lower expression), with p-values of 0.019 and 0.023, respectively. ROC analysis showed moderate diagnostic accuracy (AUC = 0.701) for miR-106a in identifying neurodegenerative status. miR-106a levels also correlated inversely with carotid intima-media thickness and brain MRI abnormalities, also reduced gastric miR-106a-5p expression is associated with systemic inflammation and neuroimaging evidence of neurodegeneration. Conclusions: While causality cannot be inferred, these findings suggest that gastric miR-106a may serve as a promising non-invasive biomarker within the gut–brain axis framework. Further longitudinal and mechanistic studies are warranted to validate its clinical utility and explore its potential role in monitoring neuroinflammatory conditions. Full article

Background/Objective: MicroRNA-21 (miR-21) is one of the most widely studied oncogenic microRNAs and has been implicated in breast cancer progression, therapy resistance, and metastatic potential. However, its utility as a long-term prognostic biomarker in patients undergoing mastectomy remains insufficiently clarified. This study evaluated the prognostic significance of miR-21 expression in predicting overall and disease-free survival. Methods: A retrospective cohort of 426 breast cancer patients who underwent mastectomy between 2010 and 2017 was analyzed. Tumor miR-21 expression was measured using quantitative real-time PCR and categorized as high or low based on cohort-derived thresholds. Long-term outcomes were assessed over a median follow-up of 112 months. Kaplan–Meier survival curves, log-rank tests, and multivariable Cox proportional hazards models were used to estimate associations between miR-21 levels and survival outcomes. Results: High miR-21 expression was identified in 48.8% of cases. Patients with high miR-21 demonstrated significantly poorer overall survival (10-year OS: 61.4% vs. 82.7%; log-rank p < 0.001) and disease-free survival (10-year DFS: 54.9% vs. 78.3%; log-rank p < 0.001). In multivariable analysis, high miR-21 remained an independent predictor of decreased OS (HR = 2.18; 95% CI: 1.56–3.04) and DFS (HR = 2.44; 95% CI: 1.78–3.33). Conclusions: Elevated miR-21 expression is a significant independent biomarker of adverse long-term prognosis in breast cancer patients undergoing mastectomy. Integrating miR-21 into postoperative risk stratification may improve individualized management strategies. Full article

Non-small cell lung cancer (NSCLC) remains a major cause of cancer-related mortality, with poor survival outcomes despite advances in surgery, chemotherapy, targeted therapy, and immunotherapy. The tumor microenvironment (TME) plays a central role in sustaining tumor growth, immune evasion, and systemic metabolic dysfunction. In this study, we performed an integrative analysis of differentially expressed microRNAs (miRNAs) to uncover their contributions to dysregulated signaling networks in NSCLC. hsa-miR-486-5p was identified as a prominent differentially expressed candidate miRNA. Using mathematical modeling and regression-based reduction, we identified Forkhead Box O1 (FOXO1) and Unc-51 like Autophagy Activating Kinase 2 (ULK2) as critical regulatory nodes that integrate oncogenic signaling with cellular homeostasis. Aberrant expression of hsa-miR-486-5p was found to modulate pathways including PI3K/AKT/mTOR, NF-κB, and JAK-STAT3, thereby promoting tumor progression and secretion of inflammatory cytokines. These cytokines, viz., IL-6, TNF-α, and IL-1β, activate muscle-specific protein degradation pathways through E3 ubiquitin ligases TRIM63 and FBXO32, linking NSCLC progression to cancer-associated sarcopenia. Quasipotential landscape analysis further revealed dynamic phenotypic transitions between stable and unstable states, highlighting the adaptability of tumor–host interactions. Collectively, our findings demonstrate that miRNA-mediated regulatory networks not only drive NSCLC progression and inflammation but also contribute to systemic muscle wasting. These insights emphasize the need for novel therapeutic strategies, including RNA-based interventions, to overcome resistance, improve survival, and address the metabolic complications associated with NSCLC. Full article

Breast cancer remains a leading cause of cancer-related mortality worldwide, with epigenetic mechanisms like N⁶ methyladenosine (m⁶A) modification playing a crucial role in tumorigenesis. The interaction between microRNAs and m⁶A regulators, such as the methyltransferase METTL14, is increasingly recognized as a key pathway in oncogenesis. This study investigated whether miR-30c-2-3p regulates METTL14 expression to influence global m⁶A levels and cell migration in breast epithelial (MCF12A) and breast cancer (MCF7) cell lines. Following transfection with miR-30c-2-3p mimics, successful overexpression was confirmed in both cell lines. Subsequent RT-qPCR and Western blotting analyses demonstrated that METTL14 mRNA and protein levels were significantly reduced at 24 and 48 h post-transfection (p < 0.05). Concurrently, global m⁶A RNA methylation levels decreased, with a more pronounced reduction observed in MCF12A cells (p < 0.001). Functionally, wound healing assays revealed that miR-30c-2-3p significantly inhibited migration, reducing wound closure by 30–44% in MCF7 cells and by 66–72% in MCF12A cells. These findings reveal a novel regulatory axis involving miR-30c-2-3p, METTL14, and m⁶A, suggesting that miR-30c-2-3p functions as a tumor suppressor and represents a promising biomarker and therapeutic target in breast cancer. Full article

Purpose: Prostate cancer is one of the most common malignancies in men, yet current prognostic methods remain suboptimal. Emerging evidence indicates that microRNAs (miRNAs) play critical roles in prostate cancer progression. This study aimed to identify miRNAs associated with adverse clinical outcomes by comparing miRNA expression profiles between prostate tumors with unfavorable versus favorable prognostic features. Materials and Methods: High-throughput next-generation sequencing (NGS) was used to analyze miRNA expression in formalin-fixed, paraffin-embedded prostate cancer tissue samples. Patients were classified into favorable or unfavorable prognosis groups based on risk stratification scores, Gleason grade group, and biochemical recurrence. Differentially expressed miRNAs were identified using a fold-change threshold ≥2 and a false discovery rate (FDR) <0.05. Predicted target genes and pathway analyses were conducted to generate candidate regulatory hypotheses rather than confirm mechanistic relationships. Results: Several miRNAs were differentially expressed according to prognostic category. miR-206 was significantly downregulated in high-risk tumors compared with low-risk tumors. High-Gleason-grade tumors showed reduced expression of miR-7704 and miR-4454, while miR-25-3p and let-7f-5p were upregulated. In patients with early biochemical recurrence, miR-7704 and miR-10400-5p were downregulated relative to those with prolonged recurrence-free survival. Target prediction analysis identified CPEB3, HAND1, PTAR1, and SPRYD4 as shared candidate targets, with CPEB3 emerging as a prioritized candidate supported by consistency in external datasets rather than a confirmed molecular target. Conclusions: Distinct miRNA expression patterns correlate with prostate cancer aggressiveness and clinical outcomes. miR-206, miR-7704, miR-4454, miR-25-3p, and let-7f-5p represent candidate prognostic biomarkers. Their shared target CPEB3 should be interpreted as a prioritized candidate for future investigation. Given the very small sample size and the lack of qRT-PCR and functional validation, these findings should be considered preliminary and hypothesis-generating, requiring validation in larger independent cohorts and experimental studies. Full article

Non-coding RNAs are pivotal regulators of metabolic disease pathogenesis, yet the role of microRNA-27a (miR-27a) in obesity-associated hepatic steatosis remains incompletely characterized. This study examined the functional contribution and molecular mechanism of miR-27a in regulating hepatocyte mitochondrial homeostasis and lipid metabolism. Utilizing in vivo mouse models, including low-fat diet controls, high-fat diet (HFD)-induced obesity, and gain- and loss-of-function approaches, miR-27a was found to be markedly upregulated in the serum and liver of obese mice, correlating with disrupted glucose and lipid homeostasis as well as hepatic steatosis. Mechanistically, miR-27a overexpression recapitulated HFD-induced mitochondrial dysfunction, manifested by decreased mitochondrial biogenesis and elevated reactive oxygen species (ROS) production. Conversely, genetic silencing of miR-27a restored mitochondrial integrity and mitigated lipid accumulation. In vitro experiments using HepG2 cells confirmed that miR-27a directly suppresses nuclear factor erythroid 2-related factor 2 (NFE2L2), and NFE2L2 overexpression counteracted miR-27a-induced mitochondrial damage and steatosis. Collectively, these results demonstrate that miR-27a promotes hepatic steatosis by targeting NFE2L2, leading to mitochondrial impairment and oxidative stress, highlighting miR-27a as a potential biomarker and therapeutic target for obesity-associated liver metabolic disorders. Full article

MicroRNA (miRNA) regulation plays a pivotal role in intracellular gene expression. Analysis of miRNA profiles can provide critical insights into disease states. As cancer-associated molecules reported in previous studies, miRNAs may serve as candidate classificatory features for exploratory cancer classification. This research analyzed serum miRNA data from patients with 13 solid cancer types and individuals without cancer. The study comprised two distinct analyses: first, stratifying the dataset into cancer and non-cancer groups to identify miRNAs differentially represented in cancer patients; and second, subdividing the cancer patient data into 13 predefined solid-cancer types to identify candidate miRNA features that discriminate among these cancer types. We employed seven feature-ranking algorithms to evaluate miRNA contributions in both analyses and generate feature lists. Each list was examined using an incremental feature selection method to extract essential miRNAs and build good-performing classification models. Several candidate miRNAs were identified for distinguishing pan-cancer samples from non-cancer ones: miR-4783-3p has been linked to associated with the regulation of endocrine cell differentiation, and miR-663a has been reported in hepatocellular carcinoma and thyroid carcinoma. The analysis also highlighted miRNAs that differentiate solid cancer types, including miR-629-3p, reported to be upregulated in lung and breast cancer, and miR-6087, reported to be downregulated in osteosarcoma and bladder cancer. Full article

Self-grooming is a fundamental and evolutionarily conserved behavior and is essential for removing Varroa destructor in honeybees (Apis mellifera). However, its molecular and neural regulation remains poorly understood. This study identifies a microRNA-mediated neuromodulatory pathway that governs the intensity of self-grooming behavior in A. mellifera. Comparative behavioral analyses revealed pronounced differences in grooming intensity between bees exhibiting strong (MS) and weak (MW) grooming phenotypes. Liquid chromatography detection and pharmacological experiments demonstrated that octopamine (OA) levels are significantly different between MS and MW bees, and OA enhances grooming behavior. Small RNA sequencing revealed differentially expressed miRNAs in the brains of MS versus MW bees, leading to the identification of miR-281-x as a candidate associated with OA regulation. Functional validation showed that overexpression of miR-281-x significantly reduces grooming behavior, whereas inhibition of miR-281-x enhances grooming. Mechanistically, bioinformatics prediction and experimental validation confirmed that miR-281-x directly targets the tdc2, which encodes tyrosine decarboxylase 2 in OA biosynthesis. Fluorescence in situ hybridization (FISH) revealed co-localization of miR-281-x and tdc2 in Kenyon cells of the mushroom bodies. RNAi-mediated knockdown of tdc2 significantly reduced grooming intensity and rescue experiments confirmed the miR-281-x–tdc2–OA regulatory axis. Together, our findings uncover a post-transcriptional modulatory mechanism linking a microRNA to neuromodulator-dependent behavioral plasticity, providing insight into the control of grooming intensity in honeybees. Full article

Epithelial ovarian cancer (EOC) remains a lethal malignancy requiring novel therapeutic strategies due to high recurrence and chemoresistance. This study evaluated the combined antitumor effect of metformin and the co-transfection of tumor-suppressor microRNAs miR-145 and miR-23b in A2780 and OV90 EOC cell lines using both 2D and 3D models. In monolayer cultures, our approach significantly reduced the expression of proliferation markers Ki-67 and c-MYC, and decreased cell migration and invasion in both cell lines compared to controls. In 3D spheroid models, the treatment reduced VEGF secretion and relative spheroid area in A2780 cells, significantly increasing cytotoxicity; however, OV90 spheroids exhibited marked resistance. Fluorescent miRNA tracking revealed that this resistance occurs despite successful intracellular delivery, indicating an intrinsic biological resistance conferred by the 3D microenvironment. Overall, these findings suggest that the combined administration of metformin and miRs effectively limits tumor progression, but also strongly underscore the importance of using complex 3D models to accurately evaluate therapeutic efficacy and intrinsic resistance mechanisms. Full article

Diabetes mellitus (DM) is a group of metabolic diseases characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The most common types—type 1 and type 2 diabetes—have different etiologies and pathophysiological mechanisms. Type 1 diabetes (T1DM) results from autoimmune destruction of the insulin-producing pancreatic β-cells, leading to the development of absolute insulin deficiency, whereas in type 2 diabetes (T2DM), impaired carbohydrate metabolism is primarily caused by insulin resistance and relative insulin deficiency. Current diagnostic criteria do not allow for the detection of the disease at the preclinical stage. MicroRNA (miRNA) influences post-translational regulation of gene expression by inhibiting mRNA translation and also promotes mRNA degradation. The aim of this review is to summarize current evidence on the role of microRNAs in the pathogenesis of T1DM and T2DM and to evaluate their potential as early diagnostic biomarkers and therapeutic targets. It is demonstrated that T1DM and T2DM exhibit altered expression of specific microRNAs involved in β-cell apoptosis, autoimmune inflammation, and insulin signaling. In T1DM, key miRNAs include miR-21, miR-25, miR-146a, and miR-375, which reflect β-cell destruction and the autoimmune process. In T2DM, critical roles are played by miR-9, miR-29, miR-34a, miR-103/107, miR-126, miR-143, and miR-375, which regulate insulin secretion, lipid metabolism, and tissue insulin sensitivity. Particular attention is given to microRNAs whose expression changes several years before clinical disease onset (miR-15a, miR-126, miR-375), offering opportunities for early diagnosis. Data are presented on circulating miRNAs in stable biological fluids (blood, urine). It should be emphasized, however, that the proposed microRNA panel currently represents only a potential diagnostic tool. This panel requires further validation and confirmation by clinicians in large-scale prospective studies and does not yet claim to be ready for routine clinical use. Nevertheless, the development of such a universal microRNA panel, followed by thorough clinical evaluation, has promising biomedical potential, which will not only allow for the diagnosis of diabetes at an early stage but also identify new therapeutic targets for personalized medicine. Full article

Diabetic cardiomyopathy (DC) is a serious health issue. MicroRNA-155b expression dysregulation might be involved in the fibrotic cycle in DC. L-Arginine (l-arg) is reported to have a preferable impact on the cardiovascular system. We aimed to understand the pathogenesis of DC and to detect the potential protective effect of l-arg through modulation of apoptosis, inflammation, fibrosis, and miR-155b expression. This study comprised four groups of forty adult male rats (10 rats in each group): diabetics, l-arg diabetics, l-arg, and controls. Blood glucose, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), body weight, and cardiac hypertrophy index (HW/BW ratio) were assessed. Echocardiographic assessment of left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) was done. Expressions of toll-like receptor-4 (TLR4), pro-inflammatory interleukin 1 beta (IL-1β), interleukin 6 (IL-6), anti-inflammatory interleukins (IL-4, IL-13), apoptotic markers (bcl-2, bax) and microRNA-155b were measured by real-time PCR. Myocardial light, electron microscopic and morphometric studies were performed. Results showed a significant decrease in cardiac hypertrophy (HW/BW = 0.0030 ± 0.0002 mg/g), echocardiographic parameters (LVEF = 54.12 ± 1.628% and LVFS = 20.40 ± 0.541%), hemodynamic parameters (HR = 411.0 ± 9.684 bpm, SBP/DBP = 84 ± 4.998/60 ± 3.062 mmHg) and downregulation of the expression of IL-4, IL-13, IL- 1β, IL-6 and TLR4 in the l-arg diabetic group compared to diabetic rats. Additionally, restoration of normal appearance of most cardiac myofibrils, intact blood vessels, decreased cardiac fibrosis and upregulation of bax expression were observed. Expression of microRNA-155b increased by 0.007 for each gram increase in blood glucose (>1.45, it showed 100% specificity and 96.7% sensitivity). In conclusion, microRNA-155b upregulation is associated with enhancement of the transcription of inflammatory cytokines and apoptotic genes. L-arginine may be a useful protective strategy for DC through modulation of apoptosis, inflammation, and fibrosis, in addition to regulating the expression of miR-155b. Full article

Crohn’s disease (CD) is a chronic immune-mediated inflammatory disorder characterized by transmural inflammation and a progressive course that frequently leads to structural complications such as intestinal fibrosis. Fibrostenosing disease represents a major clinical challenge, affecting up to 50% of patients over time and often requiring surgical intervention. Despite advances in anti-inflammatory therapies, no effective treatments currently exist to prevent or reverse established fibrosis. Intestinal fibrosis arises from a dysregulated tissue remodeling process driven by excessive extracellular matrix deposition and persistent activation of mesenchymal cells, particularly fibroblasts and myofibroblasts. This process is orchestrated through complex interactions between immune and non-immune cells and mediated by key signaling pathways, including transforming growth factor beta (TGF-β1) and the TL1A/DR3 axis. Genetic susceptibility, notably variants in NOD2 and other fibrosis-related genes, contributes not only to disease risk but also to phenotype progression. Epigenetic mechanisms, particularly microRNAs such as the miR-29 and miR-200 families, further modulate fibrogenesis and represent promising non-invasive biomarkers. Additionally, intestinal dysbiosis and specific microbial signatures, including reduced short-chain fatty acid-producing bacteria and the presence of adherent-invasive Escherichia coli, play a critical role in promoting fibrotic pathways. Mesenteric adipose tissue, especially creeping fat, also contributes to fibrosis through immune and metabolic signaling. Emerging biomarkers related to collagen metabolism and advances in molecular profiling are improving early detection strategies. Novel therapeutic approaches targeting fibrogenic pathways, including anti-TL1A agents, show promising preliminary results. A deeper understanding of these mechanisms is essential to develop effective antifibrotic therapies and improve long-term outcomes in CD. Full article

Background: Meningiomas exhibit considerable biological heterogeneity that is not fully captured by histopathological grading. Tissue-based molecular markers may provide complementary insight into tumor biology within routine diagnostic settings. Methods: Formalin-fixed paraffin-embedded tissue samples from 65 intracranial meningiomas and 13 non-neoplastic controls were analyzed. Aquaporin-4 (AQP4) expression was assessed using immunohistochemistry, while miR-216a, miR-320a, and LINC00461 levels were quantified by means of RT-qPCR. Expression patterns were compared across groups and evaluated in relation to histological grade. Results: AQP4 expression was significantly reduced in meningiomas compared with controls and showed a further decrease in higher-grade tumors. Although expression of miR-216a and miR-320a was also lower in tumor samples, these differences did not reach statistical significance. Correlation analysis revealed modest but significant associations between AQP4 and miR-216a, as well as between miR-216a and miR-320a. Individual markers demonstrated limited discriminatory performance; however, combined expression patterns suggested underlying molecular variability across tumor grades. Conclusions: Our findings indicate that AQP4 downregulation represents a consistent feature in meningiomas, while associated microRNA alterations may reflect coordinated but context-dependent expression patterns. Although these markers are not sufficient as standalone diagnostic tools, their combined tissue-level assessment may provide complementary information on tumor heterogeneity. These findings should be interpreted as exploratory and highlight the need for further validation in larger and mechanistic studies. Full article

Background: Postmenopausal osteoporosis is associated with cellular senescence and the accumulation of the senescence-associated secretory phenotype (SASP). While mesenchymal stem cell (MSC)-derived exosomes show tissue repair potential, the efficacy and mechanisms of MSC-derived apoptotic vesicles (apoVs) remain unclear. This study compared MSC-apoVs and exosomes in postmenopausal osteoporosis and investigated the underlying epigenetic mechanisms. Methods: Therapeutic efficacy was evaluated in an ovariectomized (OVX) mouse model and senescent human bone marrow mesenchymal stem cells (hBMMSCs). Small RNA sequencing identified differential microRNA (miRNA) cargos between vesicle types. SASP-related cytokine expression (IL-6, TNF-α, MCP-1) and pathway activation were assessed by RT-qPCR, ELISA, and Western blot. Results: MSC-apoV treatment attenuated bone loss in OVX mice and reduced SASP expression in senescent hBMMSCs to a greater extent than exosomes. Small RNA sequencing revealed that apoVs were enriched with a specific miRNA cluster, including hsa-let-7b-5p, hsa-miR-92a-3p, and hsa-miR-98-5p. Bioinformatic analyses identified BRAF and CRKL as downstream targets of this miRNA cluster, supported by reduced protein levels after apoV treatment. Subsequent molecular assays showed that apoV treatment inhibited the phosphorylation of both the MAPK (p38 and JNK) and NF-κB (p65) signaling pathways, which correlated with reduced local inflammation in the bone marrow microenvironment and preserved osteogenic differentiation capacity. Conclusions: MSC-apoVs attenuate postmenopausal osteoporosis more effectively than exosomes. This enhanced efficacy is associated with the delivery of an enriched miRNA cluster that inhibits MAPK and NF-κB signaling, together with suppression of BRAF and CRKL protein expression. ApoVs may represent a cell-free therapeutic strategy for age-related bone loss. Full article