Search Results (8,744)

Background: Despite clinical and pathological risk tools, predicting outcomes in non-muscle-invasive bladder cancer (NMIBC), particularly high-grade (HG) cases, remains challenging due to its unpredictable recurrence and progression. There is an urgent need for molecular biomarkers to enhance risk stratification and guide treatment. Methods: We assessed the prognostic potential of eight miRNAs (miR-9, miR-143, miR-182, miR-205, miR-27a, miR-369, let-7c, and let-7g) in a cohort of ninety patients with primary bladder cancer. Expression data were retrieved from our previously published studies. Kaplan–Meier’s and Cox’s regression analyses were used to evaluate the associations with overall survival (OS), metastasis-free survival (MFS), and clinical outcomes. Principal component analysis (PCA) was performed to identify informative miRNA combinations. Target gene prediction, pathway enrichment (DAVID), and drug–gene interaction mapping (DGIdb) were conducted in silico. Results: A high expression of let-7g and miR-9 was significantly associated with better OS in HG NMIBC and MIBC, respectively (p = 0.013 and p = 0.000). MiR-9 downregulation correlated with metastasis in MIBC (p = 0.018). Among all combinations, miR-205 and miR-27a best predicted intermediate-risk NMIBC progression and recurrence (r² = 0.982, p = 0.000). A functional analysis revealed that these miRNAs regulate key cancer-related pathways (MAPK, mTOR, and p53) through genes such as TP53, PTEN, and CDKN1A. Drug interaction mapping identified nine target genes (e.g., DAPK1, ATR, and MTR) associated with eight FDA-approved bladder cancer therapies, including cisplatin and gemcitabine. Conclusion: Let-7g, miR-9, miR-143, miR-182, and miR-205 emerged as promising biomarkers for outcome prediction in NMIBC. Their integration into liquid biopsy platforms could support non-invasive monitoring and personalized treatment strategies. These findings warrant validation in larger, prospective studies and through functional assays. Full article

Background: Freeze tolerance is an uncommon but highly effective strategy that allows certain vertebrates to survive prolonged exposure to subzero temperatures in a frozen, ischemic state. While past studies have characterized the metabolic and biochemical adaptations involved, including cryoprotectant accumulation and metabolic rate suppression, the contribution of post-transcriptional gene regulation by microRNAs (miRNAs) remains largely unexplored. This study investigated freeze-responsive miRNAs in cardiac tissue of the gray tree frog, Dryophytes versicolor, to better understand the molecular mechanisms that support ischemic survival and tissue preservation. Methods: Adult frogs were subjected to controlled freezing at −2.5 °C, and cardiac tissue was collected from frozen and control animals. Total RNA was extracted and analyzed via small RNA sequencing to identify differentially expressed miRNAs, followed by target gene prediction and KEGG pathway enrichment analysis. Results: A total of 3 miRNAs were differentially expressed during freezing, with significant upregulation of miR-93-5p and let-7b-5p and downregulation of miR-4485-3p. Predicted targets of upregulated miRNAs included genes involved in immune signaling pathways (e.g., cytokine–cytokine receptor interaction), steroid hormone biosynthesis, and neuroactive ligand–receptor interaction, suggesting suppression of energetically costly signaling processes. Downregulation of miRNAs targeting cell cycle, insulin signaling, and WNT pathways indicates possible selective preservation of cytoprotective and repair functions. Conclusion: Overall, these results suggest that D. versicolor employs miRNA-mediated regulatory networks to support metabolic suppression, maintain essential signaling, and prevent damage during prolonged cardiac arrest. This work expands our understanding of freeze tolerance at the molecular level and may offer insights into biomedical strategies for cryopreservation and ischemia–reperfusion injury. Full article

Preeclampsia (PE) is not merely a pregnancy complication but a clinical manifestation of underlying vascular dysfunction with long-term health implications. It is diagnosed after 20 weeks of gestation as new-onset hypertension with proteinuria or organ involvement. The condition arises from impaired placental development, particularly defective spiral artery remodeling, which leads to placental ischemia and the release of antiangiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng). These circulating factors contribute to systemic endothelial dysfunction, resulting in hypertension, inflammation, and multiorgan stress. Histopathological findings, including acute atherosis and abnormal vascular remodeling, further reflect the cardiovascular damage underlying PE. This review synthesizes emerging evidence on the vascular and histological mechanisms of PE, highlighting novel biomarkers such as microRNAs and neprilysin, and the potential of advanced diagnostic tools, including machine learning. Importantly, PE is now recognized not only as an obstetric disorder but also as an early marker of future cardiovascular disease. This paradigm shift emphasizes the need for personalized prevention strategies, close surveillance of high-risk women, and long-term cardiovascular follow-up. Pregnancy thus represents a critical window for early detection and intervention in women’s cardiovascular health. Full article

Alzheimer’s disease (AD) and major depressive disorder (MDD) are prevalent central nervous system (CNS) disorders that share overlapping symptoms but differ in underlying molecular mechanisms. Distinguishing these mechanisms is essential for developing targeted diagnostic and therapeutic strategies. In this study, we integrated multi-tissue transcriptomic datasets from brain and peripheral samples to identify differentially expressed microRNAs (miRNAs) in AD and MDD. Functional enrichment analyses (KEGG, GO) revealed that dysregulated miRNAs in AD were associated with MAPK, PI3K–Akt, Ras, and PD-1/PD-L1 signaling, pathways linked to synaptic plasticity, neuroinflammation, and immune regulation. In contrast, MDD-associated miRNAs showed enrichment in Hippo signaling and ubiquitin-mediated proteolysis, implicating altered neurogenesis and protein homeostasis. Network analysis highlighted key disease- and tissue-specific miRNAs, notably hsa-miR-1202 and hsa-miR-24-3p, with potential roles in neuronal survival and molecular network regulation. These findings suggest that miRNAs may serve as non-invasive biomarkers for diagnosis, prognosis, and treatment monitoring in both disorders. While therapeutic targeting of miRNAs offers promise, challenges such as blood–brain barrier penetration and tissue-specific delivery remain. This integrative approach provides a translational framework for advancing miRNA-based strategies in CNS disease research. Full article

Intrauterine growth restriction (IUGR) severely hinders the development of the livestock industry and impacts economic efficiency. MicroRNAs (miRNAs) participate in the epigenetic regulation of animal growth and development. Using IUGR pigs as a model, this study analyzed transcriptomic data from IUGR piglets to investigate the miRNA-mRNA regulatory network in their testes. Compared with NBW pigs, IUGR pigs exhibited reduced testicular volume, decreased weight, and abnormal testicular development. A total of 4945 differentially expressed mRNAs and 53 differentially expressed miRNAs were identified in IUGR testicular tissues, including 1748 downregulated and 3197 upregulated mRNAs, as well as 41 upregulated and 12 downregulated miRNAs. The integrated analysis of differentially expressed genes, miRNA target genes, and the miRNA-mRNA network revealed that IUGR may impair testicular development by disrupting cell cycle progression and apoptotic pathways, thereby hindering normal testicular cell growth. Furthermore, analysis of the miRNA-mRNA network indicated that miRNAs such as ssc-miR-23a, ssc-miR-29c, ssc-miR-193a-3p, and ssc-miR-574-3p could serve as potential marker miRNAs for IUGR testes, while YWHAZ, YWHAB, and PPP2CA may function as core target genes within this regulatory network. In conclusion, this study enhances our understanding of male reproduction in IUGR pigs and provides a theoretical foundation for preventing and treating IUGR-induced male reproductive disorders. Full article

Metabolically healthy (MHO) and unhealthy obesity (MUO) exhibit distinct molecular genetic mechanisms underlying metabolic disorders. Studying gene and microRNA expression in subcutaneous adipose tissue (SAT) may reveal key pathogenetic differences between these phenotypes. We compared the expression of genes (ADIPOQ, HIF1A, CCL2) and microRNAs (miR-142-3p, miR-155, miR-378) in SAT between MHO and MUO patients and assessed their association with metabolic parameters. The study included 39 obese patients (19 MHO, 20 MUO) and 10 healthy controls. SAT biopsies were analyzed using real-time PCR. Correlations with clinical and metabolic markers were evaluated. Obese patients showed decreased ADIPOQ (p = 0.039) and miR-142 (p = 0.008) expression and increased CCL2 (p = 0.004), miR-155 (p = 0.017), and miR-378 (p = 0.04) expression compared to the controls. MUO patients exhibited higher HIF1A expression (p = 0.03) and strong correlations between CCL2 and dyslipidemia (total cholesterol, triglycerides)/dysglycemia (fasting glucose) (r = 0.45, p = 0.03; r = 0.52, p = 0.01; r = 0.63, p = 0.001, respectively). miR-142 negatively correlated with fibrosis markers, while miR-378 was linked to insulin resistance. The differential gene and microRNA expression highlights the role of inflammation, hypoxia, and fibrosis in MUO pathogenesis. miR-142-3p, miR-155, and miR-378 may serve as potential biomarkers for metabolic risk stratification and therapeutic targets. Full article

Ulcerative colitis (UC) is associated with an elevated risk of colorectal cancer (CRC), driven by chronic inflammation and a distinct inflammation–dysplasia–carcinoma pathway. Conventional surveillance relies on colonoscopy and histologic assessment, but flat, multifocal dysplasia and sampling limitations challenge early detection. Tissue-based biomarkers offer promise in improving risk stratification and identifying patients at high risk for UC-associated CRC (UC-CRC). This review explores key categories of tissue biomarkers with potential clinical utility, including genetic mutations, epigenetic alterations, microRNA expression profiles, and markers of genomic instability such as telomere shortening, copy number variants, and aneuploidy. Many of these molecular alterations precede histologic dysplasia and reflect a “field effect,” suggesting their potential role in early cancer detection. Despite compelling associations between these biomarkers and neoplastic progression, most lack prospective validation and are not yet ready for routine clinical use. Future research should prioritize the development of integrated biomarker panels and validate their predictive accuracy in longitudinal UC cohorts. Molecular profiling may ultimately enable personalized, risk-adapted surveillance strategies that improve early detection while minimizing unnecessary interventions. Full article

Ensuring food security is a challenge for humans. Rice grain yield and quality must urgently be increased to overcome this challenge. MicroRNA (miRNA) is an important regulatory module in plant development and stress responses. Grain yield and quality are pleiotropic traits that employ cooperative genetic factors, including miRNA and its regulatory mechanisms. This review provides an overview of plant miRNAs and the composition and development process of rice grains. It also summarizes the research progress in miRNA regulation for agronomically important rice grain traits, providing a basis for further identifying miRNAs related to rice grain development and elucidating their regulatory mechanisms. Full article

Background/Objectives: Despite the significant advancements made in the diagnosis of lung cancer, the traditional diagnostic methods remain limited because they are often invasive, expensive, and not suitable for regular screening, creating a need for more accessible and non-invasive alternatives. In this context, the analysis of miRNAs in EVs and free circulating microRNA may be used as liquid biopsies in lung cancer to identify individuals at risk. This study aimed to compare miRNA profiles in the serum and EVs derived from lung cancer patients by focusing on Let-7a-5p and miR-21-3p. Materials and Methods: Serum and EVs were isolated from lung cancer patients and healthy controls. EVs were characterized using nanoparticle tracking analysis, electron microscopy, and Western blotting for surface markers (CD63, CD81, TSG101). Total miRNA levels were quantified in the serum and EVs, and specific miRNAs (hsa-let-7a-5p and hsa-miR-21-3p) were analyzed using RT-qPCR. Statistical analysis evaluated miRNA expression across clinicopathological features, including age, gender, smoking status, tumor stage, cancer type, and EGFR mutation status. Results: Total miRNA levels were significantly enriched in EVs compared to the serum. Let-7a-5p was downregulated in EVs from patients with advanced-stage lung cancer (Stage III–IV) compared to those with early-stage cancer and controls (p < 0.05), while no differences were observed in the serum. Conversely, miR-21-3p was significantly upregulated in EVs and serum from advanced-stage patients (p < 0.01) and in adenocarcinoma compared to squamous cell carcinoma (p < 0.05). No significant differences were observed for age, gender, or smoking status. Conclusions: Our findings highlight the differential expression of miRNAs in EVs and the serum, emphasizing the diagnostic potential of EV-associated Let-7a-5p and miR-21-3p in lung cancer. These results suggest that EVs are a more robust source for miRNA biomarkers compared to the serum. Full article

Since 2007, white-nose syndrome (WNS), caused by the fungus Pseudogymnoascus destructans, has killed millions of bats across North America by disrupting hibernation cycles, causing premature fat depletion and starvation. Little brown bats (Myotis lucifugus) from some populations persisting after WNS store larger pre-hibernation fat reserves than bats did before WNS, which may help bats survive winter starvation and mount an immune response to Pd in spring. MicroRNAs (miRNAs) are highly conserved, small, non-coding RNA molecules that regulate gene expression post-transcriptionally. Aberrant miRNA expression can affect metabolic pathways in mammals and has been linked to various diseases. If fat reserves and immune mechanisms influence survival from WNS, then miRNAs regulating metabolic and immune-related genes might affect WNS pathogenesis and bat survival. A previous study identified 43 miRNAs differentially expressed in bats with WNS. We analyzed these miRNAs for their roles in metabolism and immune-related pathways, using DIANA Tools and KEGG analysis, to determine a subset that could serve as biomarkers of pathophysiology or survival in WNS-affected bats. We identified miR-543, miR-27a, miR-92b, and miR-328 as particularly important because they regulate multiple pathways likely important for WNS (i.e., immune response, lipogenesis, insulin signaling, and FOXO signaling). As proof-of-concept, we used reverse transcription quantitative real-time PCR (RT-qPCR) to quantify the prevalence of these miRNAs in plasma samples of bats (n = 11) collected from a post-WNS population during fall fattening. All the selected miRNAs were detectable in at least some bats during fall fattening although prevalence varied among miRNAs. Future in vivo validation studies would help confirm functional roles and biomarker utility of these miRNAs for WNS-affected bats. Full article

Epigenetic regulation is critical to B cell development, guiding gene expression via DNA methylation, histone modifications, chromatin remodeling, and noncoding RNAs. In mature B cell neoplasms, particularly diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL), these mechanisms are frequently disrupted. Recurrent mutations in key epigenetic regulators such as EZH2, KMT2D, CREBBP, and TET2 lead to altered chromatin states, repression of tumor suppressor genes, and enhanced oncogenic signaling. Dysregulation of specific microRNAs (e.g., miR-155, miR-21) further contributes to pathogenesis and therapeutic resistance. In DLBCL, hypermethylation of SMAD1 and CREBBP mutations are associated with immune evasion and chemoresistance. In FL, EZH2 gain-of-function and KMT2D loss-of-function mutations alter germinal center B cell programming, while in CLL, DNA hypomethylation patterns reflect the cell of origin and correlate with clinical outcome. Targeted therapies such as the EZH2 inhibitor tazemetostat have demonstrated efficacy in EZH2-mutant FL, while HDAC and BET inhibitors show variable responses across B cell malignancies. The limitations of current epigenetic therapies reflect the complexity of targeting epigenetic dysregulation rather than therapeutic futility. These challenges nonetheless highlight the relevance of epigenetic alterations as biomarkers and therapeutic targets, with potential to improve the management of mature B cell neoplasms. Full article

Gastrointestinal (GI) cancers, particularly colorectal and gastric cancers, majorly contribute to global cancer mortality due to frequent late-stage diagnosis and poor therapeutic response in advanced disease. Earlier detection of GI cancers is needed for a better prognosis. This review examines both traditional and emerging biomarkers that contribute significantly to early detection, prognostication, and prediction of therapeutic resistance or sensitivity. Specifically, we highlight the diagnostic utility of non-invasive liquid biopsy biomarkers such as circulating tumor DNA (ctDNA), microRNAs (miRNAs), and exosomes. Moreover, we discuss the prognostic and predictive value of conventional genetic alterations, including KRAS, BRAF, and HER2. Although new findings have shown the advantages of liquid biopsy over colonoscopy, there are still limitations to the technique, such as cost-effectiveness, technological gaps in low-resource settings, and uncertain detection rates. Further studies are required to test the validity and accessibility of liquid biopsy and its biomarkers in order to advance personalized diagnosis and treatments for GI cancers. Such a study will be helpful for clinicians to better manage patients with GI cancers. Full article

Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most lethal cancers, accounting for a significant proportion of cancer-related deaths globally. Despite advancements in medical science, treatment options for PDAC remain limited, and the prognosis is often poor. Early detection is a critical factor in improving patient outcomes, but current diagnostic methods often fail to detect PDAC until it has advanced to a late stage. In this context, the development of more effective diagnostic tools is of paramount importance. In this study, we explored the potential of non-coding RNAs (ncRNAs) as diagnostic markers for PDAC using cell-free nucleotides and liquid biopsies. Leveraging the power of Next Generation Sequencing (NGS), bioinformatics analysis, and machine learning (ML), we were able to identify unique RNA signatures associated with PDAC. Our findings revealed twenty key genes, including microRNAs (miRNAs), long-non-coding RNAs (lncRNAs), and miscellaneous RNAs that demonstrated high classification accuracy. Specifically, our model achieved a classification accuracy of 87% and an area under the receiver operating characteristic curve (AUC) of 91%. These ncRNAs could potentially serve as robust biomarkers for PDAC, offering a promising avenue for the development of a non-invasive diagnostic test. This could revolutionize PDAC diagnosis, enabling earlier detection and intervention, which is crucial for improving patient outcomes. This work lays the groundwork for future research, with the potential to significantly enhance PDAC diagnosis and therapy. Full article

This study aims to investigate the molecular mechanisms underlying germ cell tumors (GCTs), focusing specifically on seminomas and teratomas. By analyzing gene expression profiles and miRNA interactions, the goal is to identify key regulatory miRNAs and signaling pathways that differentiate these tumor types and could serve as important regulators for therapy development. Raw data for seminomas and teratomas were extracted from the GEO database, and gene hubs were identified using STRING and Gephi. Signaling pathways and functional annotations were analyzed using miRPathDB, while miRNA–gene interactions were explored via miRWalk. Hub miRNAs were filtered and confirmed using miRDB. This study highlights significant changes in gene expression diversity between tumor and normal gonadal tissues, providing insights into the molecular dynamics of seminomas and teratomas. Distinctions between seminomas and teratomas were identified, shifting the focus toward miRNAs to discover more precise and novel therapeutic approaches. The hub genes of seminomas and teratomas were identified separately. MiRNAs targeting these hub genes were also determined and confirmed. These miRNAs collectively influence essential oncogenic pathways—confirming hsa-miR-138-5p as a regulator of pathways such as Hippo signaling, transcriptional misregulation in cancer, and microRNA cancer signaling in seminomas, and hsa-miR-200b-3p as a regulator of p53 signaling, T cell receptor signaling, and pathways including PI3K/AKT, MAPK/ERK, and Wnt/β-catenin in teratomas—confirming their potential as promising candidates for subtype-specific therapeutic intervention. MiRNAs identified through bioinformatics analyses, and their predicted regulatory roles in key oncogenic pathways, represent potential therapeutic targets or regulators of biological processes. However, further experimental validation is needed to confirm these findings. Full article

Background/Objectives: Despite advances in diagnosis and treatment, colorectal cancer (CRC) remains one of the most prevalent and challenging malignancies worldwide. The dysregulation of microRNAs (miRNAs) has emerged as a critical factor in CRC onset, progression, and therapeutic resistance. This study aims to provide an overview of global research trends on miRNAs in CRC, (i) identifying the most studied miRNAs, (ii) exploring under-investigated areas, and (iii) highlighting emerging themes and potential future directions. Methods: To assess the evolution of the global miRNA–CRC research trends, we conducted a bibliometric analysis of 828 CRC–miRNA-focused articles published between 2008 and 2024, sourced from the Scopus database. Bibliometric mapping was performed using the R/Bibliometrix package and by leveraging a customized Python-based pipeline, which is useful for extracting and validating miRNA identifiers (miRNA IDs) based on the miRBase database. This miRNA ID-related approach enabled us to systematically identify the most frequently studied miRNAs over time while highlighting underexplored miRNA. Results: The analysis revealed a substantial and accelerating publication growth rate, delineating three major phases in CRC–miRNA research. China emerged as the leading contributor in terms of the publication volume. miR-21, miR-34a, and miR-195-5p were among the most frequently studied miRNAs, underscoring their relevance to CRC biology and therapy. Keyword and citation analyses identified key thematic areas, such as cell proliferation, epithelial–mesenchymal transition, and chemoresistance, especially to oxaliplatin and 5-fluorouracil. Emerging research frontiers included ferroptosis, ceRNA networks, and exosome-mediated miRNA transport. An analysis of the collaborations indicated strong intra-national collaborations, with room for expanding international research networks. Conclusions: This study provides an in-depth bibliometric landscape of the CRC-related miRNA research by highlighting influential studies and journals while identifying gaps and underexplored topics. These insights offer valuable guidance for future translational and clinical research on this topic. Full article