Non-coding RNA Research最新文献

{"title":"Overview of small proteins encoded by bacterial dual-function small RNAs","authors":"Xia Cai ,&nbsp;Hui Shan ,&nbsp;Jiaojiao Wang ,&nbsp;Jiaxin Qin ,&nbsp;Huiling Gong ,&nbsp;Jun Cai ,&nbsp;Jin He","doi":"10.1016/j.ncrna.2025.07.002","DOIUrl":"10.1016/j.ncrna.2025.07.002","url":null,"abstract":"<div><div>Small RNAs (sRNAs) are widely used by bacteria to regulate diverse biological processes. Although they are generally considered “non-coding”, some sRNAs (called dual-function sRNAs) have been found to encode small proteins, which are usually less than 50 amino acids in length and have long been overlooked due to significant challenges in their annotation and biochemical detection. However, in the past few decades, an increasing number of small proteins encoded by dual-function sRNAs have been reported. Previous reviews of dual-function sRNAs have mainly focused on their base-pairing nucleic acid functions, with less emphasis on the nature of their translated peptides, resulting in limited understanding of their full functional scope. This article reviews ten small proteins encoded by dual-function sRNAs and introduces their physiological functions, interacting protein partners, and the research methods used, aiming to provide new perspectives and directions for the study of small proteins and enhance understanding of bacterial regulatory mechanisms mediated by dual-function sRNAs.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"15 ","pages":"Pages 44-50"},"PeriodicalIF":5.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aerobic exercise alleviates allergic airway inflammation by suppressing circMETTL9-mediated formation of macrophage extracellular traps","authors":"Haixia Wang ,&nbsp;Ting Gao ,&nbsp;Bin Ma ,&nbsp;Yuanmin Jia ,&nbsp;Hui Wei ,&nbsp;Danyang Li ,&nbsp;Junlian Gu ,&nbsp;Ou Chen ,&nbsp;Shouwei Yue","doi":"10.1016/j.ncrna.2025.08.008","DOIUrl":"10.1016/j.ncrna.2025.08.008","url":null,"abstract":"<div><div>Emerging evidence suggests that aerobic exercise exerts beneficial effects on asthma. Previous studies have demonstrated that cell communication can drive the formation of macrophage extracellular traps (METs). However, the potential of aerobic exercise to mediate communication between airway epithelial cells and macrophages, thereby influencing MET formation, remains unexplored. Our data reveal that the upregulation of circular RNA <em>METTL9</em> (<em>circMETTL9</em>), derived from methyltransferase-like protein 9 (<em>METTL9</em>) in airway epithelial cells, promotes the formation of METs. Notably, aerobic exercise was found to downregulate the expression of <em>circMETTL9</em>, thereby facilitating communication between airway epithelial cells and macrophages and inhibiting METs formation. Mechanistically, <em>circMETTL9</em> and insulin-like growth factor binding protein 3 (IGFBP3) compete for binding to the DEXDc domain of eukaryotic translation initiation factor 4A3 (EIF4A3), which regulates METs via the C-X-C motif chemokine ligand 12(CXCL12) -C-X-C chemokine receptor type 4(CXCR4) signaling axis. This study provides robust molecular evidence supporting aerobic exercise as a foundational pulmonary rehabilitation strategy for lung protection in asthma. Targeting <em>circMETTL9</em>, mimicking this exercise-mediated pathway, represents a promising therapeutic approach. These insights offer a direct mechanistic rationale for refining exercise-based rehabilitation protocols and developing novel targeted therapies.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"15 ","pages":"Pages 156-171"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of plasma tRNA-derived small RNA i-tRF-15:31-Lys-CTT-1 as a biomarker for diagnosis and prognosis of pulmonary arterial hypertension","authors":"Yusi Chen ,&nbsp;Tengteng Zhu ,&nbsp;Fang Li ,&nbsp;Yingjie Tan ,&nbsp;Tianyu Wang ,&nbsp;Xiaoqin Luo ,&nbsp;Jun Luo ,&nbsp;Yi Tang ,&nbsp;Jianqiang Peng ,&nbsp;Jiang Li","doi":"10.1016/j.ncrna.2025.08.002","DOIUrl":"10.1016/j.ncrna.2025.08.002","url":null,"abstract":"<div><h3>Introduction</h3><div>tRNA-derived small RNAs (tsRNAs) are emerging as noninvasive biomarkers of cellular damage. However, their role in pulmonary arterial hypertension (PAH) remains unclear.</div></div><div><h3>Methods</h3><div>Plasma i-tRF-15:31-Lys-CTT-1 levels were quantified in a discovery cohort (n = 141 PAH patients; n = 50 controls) and a verification cohort (n = 254 PAH patients; n = 70 controls). Diagnostic performance was assessed using receiver operating characteristic analysis, and survival outcomes were evaluated with Kaplan-Meier curves and multivariable Cox regression models.</div></div><div><h3>Results</h3><div>In discovery cohort, the median age was 41 years (IQR 27–54), with 65.9 % female and a median REVEAL 2.0 score of 7 (IQR 6–8). In verification cohort, the median age was 36 years (IQR 31–52), with 63.4 % female and a median REVEAL 2.0 score of 6 (IQR 4–7). i-tRF-15:31-Lys-CTT-1 showed the greatest fold change among tsRNAs in idiopathic PAH (P &lt; 0.0001). Levels of i-tRF-15:31-Lys-CTT-1 were significantly lower in the high-risk REVEAL group (P &lt; 0.0001). The area under the curve (AUC) of i-tRF-15:31-Lys-CTT-1 for idiopathic PAH diagnosis was 0.90 in discovery cohort and 0.81 in verification cohort. Kaplan-Meier analysis revealed that lower i-tRF-15:31-Lys-CTT-1 levels correlated with poorer prognosis (P &lt; 0.0001). After adjusting for age, sex, and BMI, patients in the highest quartile had a significantly lower incidence of clinical events compared to those in the lowest quartile (HR = 0.08; 95 % CI 0.032–0.18; P &lt; 0.001). Incorporating i-tRF-15:31-Lys-CTT-1 into the REVEAL 2.0 model improved predictive accuracy (AUC from 0.67 to 0.75, P &lt; 0.0001).</div></div><div><h3>Conclusions</h3><div>i-tRF-15:31-Lys-CTT-1 levels are decreased in PAH, correlate with disease severity, and are promising to improve clinical diagnosis and risk stratification.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"15 ","pages":"Pages 108-119"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144864570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging roles of tsRNAs in programmed cell death and disease therapeutics: challenges, opportunities, and future directions","authors":"Zhe Li ,&nbsp;Bo Zhang ,&nbsp;Yanru Pan ,&nbsp;Qiuyan Weng ,&nbsp;Kefeng Hu","doi":"10.1016/j.ncrna.2025.07.003","DOIUrl":"10.1016/j.ncrna.2025.07.003","url":null,"abstract":"<div><div>Programmed cell death (PCD), which includes various forms such as apoptosis, autophagy, necroptosis, pyroptosis, and ferroptosis, plays a pivotal role in disease pathogenesis and progression. tRNA-derived small RNAs (tsRNAs) have emerged as crucial regulators of these processes, influencing cellular fate and disease outcomes. Research has revealed diverse expression profiles of tsRNAs across various diseases, emphasizing their roles in modulating PCD pathways and their potential value in diagnosis and treatment. Specific tsRNAs can either promote or inhibit apoptosis; for example, tsRNA-3043a promotes ovarian granulosa cell apoptosis in premature ovarian insufficiency, whereas tsRNA-04002 prevents apoptosis in nucleus pulposus cells to delay intervertebral disc degeneration. Furthermore, tsRNAs serve as potential biomarkers for early disease detection, with emerging detection technologies enhancing their clinical utility. Therapeutically, tsRNA-targeted strategies, such as RNA interference and exosome-based drug delivery, offer new avenues for modulating PCD in diseases such as cancer, cardiovascular disorders, and neurodegenerative diseases. Despite challenges in understanding tsRNA biogenesis and functional diversity, their roles in regulating PCD highlight their strong potential in advancing disease diagnostics, treatment strategies, and personalized medicine.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"15 ","pages":"Pages 65-73"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144772509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"5′tiRNA-Glu-TTC targets TRPV3 and activates the PI3K/AKT signaling pathway to modulate skin photoaging","authors":"Zhuohong Xu ,&nbsp;Lihao Liu ,&nbsp;Xiaoxi Dai ,&nbsp;Xuyue Zhou ,&nbsp;Lihao Chen ,&nbsp;Hongying Chen ,&nbsp;Chao Luan ,&nbsp;Dan Huang ,&nbsp;Jiaan Zhang ,&nbsp;Yu Hu ,&nbsp;Kun Chen ,&nbsp;Heng Gu","doi":"10.1016/j.ncrna.2025.07.004","DOIUrl":"10.1016/j.ncrna.2025.07.004","url":null,"abstract":"<div><div>tRNA-derived small RNAs (tsRNAs), a class of non-coding RNAs (ncRNAs), have garnered increasing research interest for their potential roles in various biological processes. Among these, 5′tiRNA-Glu-TTC has been implicated in aging, but its role in skin photoaging remains elusive. This study aimed to elucidate the impact of 5′tiRNA-Glu-TTC on skin photoaging. RT-qPCR analysis revealed that 5′tiRNA-Glu-TTC expression increased in human dermal fibroblasts (HDFs), human skin tissues, and mouse skin tissues following UVB irradiation. In HDFs, transfection of a 5′tiRNA-Glu-TTC mimic induced photoaging phenotypes, while its inhibitor alleviated UVB-induced photoaging. This study found that 5′tiRNA-Glu-TTC participates in photoaging through binding to TRPV3. Overexpression of TRPV3 rescued the photoaging effects induced by the 5′tiRNA-Glu-TTC mimic. Furthermore, 5′tiRNA-Glu-TTC influences photoaging also by activating the PI3K/AKT signaling pathway, an effect that was reversed by TRPV3 overexpression. In vivo studies in nude mice showed that intradermal injection of 5′tiRNA-Glu-TTC adeno-associated virus alleviated UVB-induced skin aging phenotypes, including epidermal thickening, dermal collagen reduction, and increased transepidermal water loss (TEWL). Collectively, our findings demonstrate that 5′tiRNA-Glu-TTC mediates photoaging by targeting TRPV3 and activating the PI3K/AKT pathway.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"15 ","pages":"Pages 29-43"},"PeriodicalIF":5.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA MIR155HG suppresses cell apoptosis by activating autophagy via miR-7036b-3p/GPNMB axis and AMPK/mTOR signaling in spinal cord injury","authors":"Ruoxi Liu ,&nbsp;Jintao Ye ,&nbsp;Sihua Huang","doi":"10.1016/j.ncrna.2025.05.013","DOIUrl":"10.1016/j.ncrna.2025.05.013","url":null,"abstract":"<div><h3>Background</h3><div>Long non-coding RNAs (lncRNAs) participate in spinal cord injury (SCI) development through regulating autophagy and neuronal apoptosis. Previously, <em>MIR155HG</em> was identified as an upregulated lncRNA in rat bladder tissues harvested after SCI operation. Our study aimed to elucidate the function of <em>MIR155HG</em> in SCI.</div></div><div><h3>Methods</h3><div>Glutamate (Glu)-stimulated primary mouse spinal cord neurons were used as SCI cellular models. Contusion-induced SCI mouse models were established using an improved weightlessness method. Neuronal apoptosis and autophagy affected by <em>MIR155HG</em> or <em>GPNMB</em> silencing were assessed by TUNEL staining, flow cytometry assay, western blotting, and immunofluorescence staining. The binding of miR-7036b-3p on <em>MIR155HG</em> (or <em>GPNMB</em>) was verified by luciferase reporter assay. Histological changes were observed through HE and Masson staining.</div></div><div><h3>Results</h3><div><em>MIR155HG</em> and <em>GPNMB</em> expression was elevated while miR-7036b-3p expression was reduced in SCI. <em>MIR155HG</em> silencing attenuated the apoptosis in Glu-stimulated neurons and ameliorated glial scar formation and motor function of SCI mice. <em>GPNMB</em> knockdown mitigated apoptosis, enhanced autophagy, activated AMPK phosphorylation, and repressed mTOR phosphorylation. <em>MIR155HG</em> upregulated <em>GPNMB</em> expression by sponging miR-7036b-3p. The autophagy inhibitor 3-MA reversed the above changes caused by <em>GPNMB</em> depletion.</div></div><div><h3>Conclusion</h3><div><em>MIR155HG</em> knockdown alleviated neuronal apoptosis by enhancing autophagy in SCI via miR-7036b-3p/<em>GPNMB</em> axis and AMPK/mTOR pathway.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"15 ","pages":"Pages 1-17"},"PeriodicalIF":5.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144623537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-viral HCC miRNA profiling reveals miR-1972 as a potential positive prognostic marker","authors":"Venkata Ramana Mallela ,&nbsp;Marie Rajtmajerová ,&nbsp;Esraa Ali ,&nbsp;Lenka Červenková ,&nbsp;Andriy Trailin ,&nbsp;Petr Hošek ,&nbsp;Richard Pálek ,&nbsp;Ondřej Daum ,&nbsp;Václav Liška ,&nbsp;Kari Hemminki ,&nbsp;Filip Ambrozkiewicz","doi":"10.1016/j.ncrna.2025.07.006","DOIUrl":"10.1016/j.ncrna.2025.07.006","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Hepatocellular carcinoma (HCC) is the third deadliest cancer worldwide. Its high mortality is primarily attributed to late-stage diagnosis. While mutations in driver genes, such as those encoding β-catenin (CTNNB1), tumor protein p53 (TP53), and telomerase reverse transcriptase promoter (TERTp) are well-documented in the literature, dysregulation of microRNAs (miRNAs), small non-coding RNAs that serve as crucial translational regulators, remains poorly understood.</div></div><div><h3>Methods</h3><div>We conducted microRNA profiling by microarrays in 45 paired (tumor and non-tumor adjacent tissue) samples from non-viral HCC patients. We performed clinical correlation, ROC analysis and survival analysis of time to recurrence (TTR), disease-free survival (DFS) and overall survival.</div></div><div><h3>Results</h3><div>We identified 23 significantly dysregulated miRNAs (p ≤ 0.05, fold change ≥2). We investigated their differential expression and its relationship with clinical and pathological variables. Further, we found that miRNA-1972 may serve as an important positive prognostic marker because its high levels were associated with longer TTR and DFS. Significant positive results were obtained in receiver operating characteristic analysis for miR-1972, miR-3651 and miR-486–5p.</div></div><div><h3>Conclusion</h3><div>miRNA-1972 is a strong prognostic marker in non-viral HCC. Dysregulation of several other miRNAs relates to pathological variables such as amount of stroma within tumor, microvascular invasion and micronodularity.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"15 ","pages":"Pages 100-107"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-129-1-3p down-regulation promotes BAG cochaperone 3 (BAG3)-driven pro-fibrotic processes in primary fibroblasts from patients with recessive dystrophic epidermolysis bullosa","authors":"Rebecca Nobili ,&nbsp;Cristina Barbagallo ,&nbsp;Marco Ragusa ,&nbsp;Jasmine Genovese ,&nbsp;Valentina D'Agostino ,&nbsp;Andrea Diociaiuti ,&nbsp;Daniele Castiglia ,&nbsp;Teresa Odorisio ,&nbsp;Giovanna Zambruno ,&nbsp;May El Hachem ,&nbsp;Angelo Giuseppe Condorelli","doi":"10.1016/j.ncrna.2025.08.005","DOIUrl":"10.1016/j.ncrna.2025.08.005","url":null,"abstract":"<div><div>Recessive dystrophic epidermolysis bullosa (RDEB) is a rare and severe skin fragility disease due to loss-of-function mutations in the <em>COL7A1</em> gene. RDEB patients suffer from relentless mucocutaneous blisters that evolve into chronic wounds with inflammation and progressive fibrosis, which heavily impacts the disease course. RDEB-associated fibrosis is the result of a complex dialogue among different cell types, signalling pathways and epigenetic players that are still poorly characterized. The expression levels of over 750 mature microRNAs were investigated in primary fibroblasts from patients with RDEB (RDEB-FBs) and healthy donors using TaqMan Low-Density Arrays. Among deregulated molecules, only the miR-129-1-3p was down-regulated in RDEB-FBs. Therefore, the role of miR-129-1-3p in regulating the fibrotic features of RDEB-FBs was explored by biochemical and functional assays in cells transfected with a miR-129-1-3p mimic or a small interfering RNA specific for BAG3 (BAG cochaperone 3), a newly identified miR-129-1-3p target. BAG3 expression levels were significantly increased in RDEB-FBs grown under basal conditions and reduced in response to their transfection with a miR-129-1-3p mimic. In RDEB-FBs, the over-expression of miR-129-1-3p or BAG3 silencing markedly impaired cell contractility, a typical feature of activated/pro-fibrotic fibroblasts, decreased phospho-AKT (Ser473) levels, and reduced the ability to synthetize and deposit collagen in the extracellular matrix. Treatment of patients' fibroblasts with the AKT inhibitor perifosine (KRX-0401) recapitulated the effects observed with the mimic molecule of miR-129-1-3p and BAG3 silencing. Our results highlight the role of the miR-129-1-3p/BAG3/AKT axis in RDEB pathogenesis, complementing and expanding the knowledge on non-coding RNAs involved in fibrosis-related processes. Taken together, these findings may contribute to enlarge the toolkit of molecules and pathways that can be exploited as therapeutic targets in skin fibrosis.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"15 ","pages":"Pages 142-155"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144931923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progenitor cells, microglia, and non-coding RNAs: Orchestrators of glioblastoma pathogenesis and therapeutic resistance","authors":"Adil Husain ,&nbsp;Firoz Ahmad ,&nbsp;Sandeep Pandey ,&nbsp;Tarun Kumar Upadhyay ,&nbsp;Sojin Kang ,&nbsp;Min Choi ,&nbsp;Jinwon Choi ,&nbsp;Moon Nyeo Park ,&nbsp;Bonglee Kim","doi":"10.1016/j.ncrna.2025.07.007","DOIUrl":"10.1016/j.ncrna.2025.07.007","url":null,"abstract":"<div><div>Glioblastoma (GB) remains a major challenge owing to its extremely aggressive nature and resistance to conventional therapies. This review focuses on the intricate roles of progenitor cells, microglia, and non-coding RNAs (ncRNAs) in orchestrating GB pathogenesis and therapy resistance. Glioma stem cells (GSCs), derived from progenitor cells, are important drivers of tumor initiation and recurrence and exhibit remarkable plasticity and resistance to treatment. Microglia, the immune cells of the brain, are hijacked by GB cells to create an immunosuppressive microenvironment that supports tumor growth and resistance to therapy. Non-coding RNAs, including microRNAs and long noncoding RNAs, regulate multiple resistance mechanisms by modulating gene expression and influencing the interactions between progenitor cells and microglia. This review highlights new insights into these interconnected signaling pathways and explores potential therapeutic strategies targeting these molecular players to overcome treatment resistance and improve outcomes in patients with GB.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"15 ","pages":"Pages 85-99"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144852387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miRNA-195-5p modulates cell proliferation and stemness by targeting the Wnt signalling network in breast cancer","authors":"Sanjeev Kumar ,&nbsp;Neeru Saini","doi":"10.1016/j.ncrna.2025.09.001","DOIUrl":"10.1016/j.ncrna.2025.09.001","url":null,"abstract":"<div><div>Cancer stem cells (CSCs) are a specific subpopulation of cells within the tumour characterised by self-renewal, proliferation and tumorigenic potential. Heterogeneity in the CSCs population and their ability to rewire the signalling networks make it difficult to target cancer by single gene inhibition. This study investigates the regulatory role of miR-195-5p in modulating CSC properties and associated signalling pathways in breast cancer. Previously shown to inhibit proliferation, invasion, and metastasis, miR-195-5p is now revealed to downregulate stemness markers (OCT4, SOX2, NANOG, and CD44). The prevalence of heterogeneity of stemness markers in MCF-7 and MDA-MB-231 cell lines is a novel advancement of this study. In MCF-7, SOX2-and CD44-overexpressing cells were found to be distinct, non-overlapping populations, as confirmed by immunofluorescence colocalisation analysis. SOX2-positive nuclei comprised ∼30 % of the MCF-7 population and were significantly reduced following miR-195-5p overexpression. Mechanistically, this downregulation of stemness correlated with decreased expression of β-catenin and its upstream regulators GSK3β and FZD6, were validated as direct targets of miR-195-5p using a luciferase reporter assay. miR-195-5p also inhibited TCF/LEF transcriptional activity, indicating suppression of canonical Wnt/β-catenin signalling. Functionally, miR-195-5p overexpression led to a reduced proliferation zone in CFSE-prestained 3D spheres derived from MCF-7 cells over seven days. To further dissect its mechanism, Wnt signalling was perturbed using siRNA against GSK3β, β-catenin and ICG-001 (a CBP/β-catenin interaction inhibitor), and their combination. GSK3β knockdown led to increased β-catenin expression, nuclear localisation, and enhanced 3D sphere proliferation, while β-catenin inhibition upregulated protein expression of GSK3β and suppressed proliferation of cancer cells. Combined inhibition of GSK3β and CBP/β-catenin interaction downregulated expression of β-catenin, supporting the role of miR-195-5p in CSC suppression. This study identifies miR-195-5p as a potent regulator of CSCs and proliferation, and modulator of the Wnt signalling cascade. Co-inhibition of GSK3β and CBP/β-catenin through miR-195-5p highlights its therapeutic potential in combating stemness and proliferation in breast cancer.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"15 ","pages":"Pages 172-181"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}