Non-coding RNA Research最新文献

{"title":"TPR is required for circRNA, lncRNA and mRNA nuclear export","authors":"Min Zhou ,&nbsp;Ruirui Jia ,&nbsp;Mengya Gao ,&nbsp;Jun Yang ,&nbsp;Hongbo Qi","doi":"10.1016/j.ncrna.2025.11.010","DOIUrl":"10.1016/j.ncrna.2025.11.010","url":null,"abstract":"<div><h3>Background</h3><div>Efficient RNA nuclear export is essential for proper cellular function and normal physiology, with defects in this process leading to pathological consequences. Our study aimed to investigate the role of translocated promoter region (TPR), nuclear basket protein, in orchestrating RNA transport in human cells as well as the function of TPR-mediated RNA nuclear export in cervical cancer cells.</div></div><div><h3>Methods</h3><div>RNA sequencing and bioinformatic analysis were applied to explore the effect of TPR on circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and mRNAs nuclear export and their corresponding sequence characteristic. Fluorescence in situ hybridization was employed to explore the role of TPR in RNA nuclear export. Immunofluorescence staining was used to study the role of TPR in R-loop and DNA damage. Flow cytometry assay was applied to investigate the influence of TPR on cell cycle in cervical cancer cells.</div></div><div><h3>Results</h3><div>TPR depletion leads to the nuclear accumulation of 7243 circRNAs, 1913 lncRNAs, and 2758 mRNAs. Codepletion and rescue experiments suggested that the modulation of TPR-mediated circRNAs nuclear export might be independent of XPO4. The regulation of TPR-mediated circRNAs nuclear export is independent of circRNAs characteristics, while, the regulation of TPR-mediated lncRNAs and mRNAs nuclear export is partly dependent on lncRNAs/mRNAs transcription length. Moreover, the lack of TPR results in nuclear R-loop accumulation, causing DNA damage and cell cycle arrest as well as subsequent inhibition of cell proliferation in cervical cancer cells.</div></div><div><h3>Conclusions</h3><div>This study highlights the nuclear export of circRNA, lncRNA and mRNA relies critically on TPR, a mechanism that may inhibit nuclear accumulation of R-loop and DNA damage in cervical cancer cells.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"17 ","pages":"Pages 32-43"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145692652","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":"The progress of m6A methylation-regulated non-coding RNAs in osteogenic differentiation and osteoporosis","authors":"Yongbin Wang ,&nbsp;Baicheng Ma ,&nbsp;Jiashuo Qiu ,&nbsp;Likun Yu ,&nbsp;Jianjun Xiong ,&nbsp;Qianfu Yu ,&nbsp;Xingnuan Li ,&nbsp;Haichun Liao ,&nbsp;Youen Huang ,&nbsp;Shan He","doi":"10.1016/j.ncrna.2025.11.005","DOIUrl":"10.1016/j.ncrna.2025.11.005","url":null,"abstract":"<div><div>N6-methyladenosine (m6A) is the most abundant internal modification of eukaryotic RNA, and has increasingly been recognized as a critical regulator of gene expression at both the transcriptional and post-transcriptional levels. The m6A modification process is highly dynamic and reversible, governed by methyltransferase writers (e.g., METTL3, METTL14, WTAP), demethylase erasers (such as FTO and ALKBH5), and specific readers (including YTHDF and IGF2BP protein families) that interpret the modification and mediate its downstream effects. Accumulating evidence indicates that m6A-mediated regulation of non-coding RNAs (ncRNAs) plays a pivotal role in osteogenic differentiation, a process central to bone formation. Impaired osteogenesis, which contributes to decreased bone mass, is closely linked to the onset and progression of osteoporosis. This review summarizes recent progress on the interplay between m6A modification and ncRNAs in osteogenic differentiation, and outlines a regulatory framework, the m6A-ncRNA-target gene axis, that includes m6A modification, ncRNA interactions, and downstream signaling pathways, such as Wnt/β-catenin and BMP/Smad, and discusses their potential as biomarkers or therapeutic targets for osteoporosis, with the goal of providing new insights into the epigenetic mechanisms underlying osteoporosis and to identify potential molecular targets for future therapeutic strategies.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"17 ","pages":"Pages 1-11"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645799","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":"circ_0103896/miR-432–5p/FTO feedback loop suppresses the formation and progression of intracranial aneurysm","authors":"Zhiwen Lu ,&nbsp;Shijie Zhu ,&nbsp;Yina Wu ,&nbsp;Fengfeng Xu ,&nbsp;Qinghai Huang","doi":"10.1016/j.ncrna.2025.11.001","DOIUrl":"10.1016/j.ncrna.2025.11.001","url":null,"abstract":"<div><div>Circular RNAs (circRNAs) and m⁶A RNA methylation play crucial roles in the pathogenesis of intracranial aneurysm (IA); however, their regulatory interplay remains unclear. Through circRNA profiling of 16 IA tissues and 8 superficial temporal arteries, we identified hsa_circ_0103896 as significantly downregulated in IA. RT-qPCR analysis further revealed that decreased circ_0103896 or increased miR-432–5p expression correlated with IA progression. Functional assays demonstrated that circ_0103896 inhibited the phenotypic switch of human brain vascular smooth muscle cells (hBVSMCs) from a contractile to a synthetic state, whereas circ_0103896 knockdown reversed this effect. <em>In vivo</em>, circ_0103896 overexpression alleviated IA severity, whereas its depletion aggravated aneurysm formation. Mechanistically, circ_0103896 functioned as a sponge for miR-432–5p, thereby upregulating FTO, which in turn promoted m⁶A demethylation of circ_0103896. This process reinforced circ_0103896 expression, forming a positive feedback loop. The circ_0103896/miR-432–5p/FTO axis thus suppresses hBVSMC phenotypic transformation and mitigates IA progression. These findings reveal a novel epigenetic mechanism involving m⁶A modification and circRNA–miRNA crosstalk in IA pathogenesis, highlighting circ_0103896 as a potential therapeutic target.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"17 ","pages":"Pages 59-75"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797816","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":"Mechanistic roles of long non-coding RNAs in gastric cancer therapy resistance","authors":"Jiayi Chen ,&nbsp;Juanmei Gao","doi":"10.1016/j.ncrna.2025.12.004","DOIUrl":"10.1016/j.ncrna.2025.12.004","url":null,"abstract":"<div><div>Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide. While gastrointestinal tumor screening has reduced incidence and mortality, its treatment faces is hindered by challenges including chemotherapy resistance and poor prognosis. Long non-coding RNAs (lncRNAs), a class of non-coding RNAs exceeding 200 nucleotides in length, serve as pivotal regulators in GC pathogenesis and therapeutic resistance. This review comprehensively summarizes the mechanistic roles of lncRNAs in chemotherapy, immunotherapy, and targeted therapy resistance for GC. In chemotherapy, lncRNAs modulate drug sensitivity to fluoropyrimidines (5-FU), platinum-based agents and other chemotherapeutics by regulating autophagy, apoptosis, metabolic reprogramming and DNA damage repair mechanisms, such as HNF1A-AS1, LINC00942 and CRNDE. In immunotherapy, lncRNAs influence immune checkpoint inhibitor efficacy by regulating PD-L1 expression, tumor microenvironment (TME), and macrophage polarization (e.g., LINC01094, MIR4435-2HG). Notably, specific lncRNAs (e.g., LINC00665, HOTAIR) contribute to resistance against HER2-targeted and anti-angiogenic therapies. Although current research remains exploratory, lncRNAs show significant promise as predictive biomarkers and therapeutic targets. Future personalized strategies intergrating lncRNA profiles could help overcome drug resistance and improve patient outcomes.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"17 ","pages":"Pages 150-159"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938657","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":"Circadian rhythm-related miR-6883-5p suppresses enzalutamide-resistant prostate cancer","authors":"Wenchang Yue ,&nbsp;Chao Li ,&nbsp;Tao Wang ,&nbsp;Jiawei You ,&nbsp;Jiale Sun ,&nbsp;Jiapeng Liu ,&nbsp;Ashutosh K. Tewari ,&nbsp;Kyprianou Natasha ,&nbsp;Mariana G. Figueiro ,&nbsp;Jianquan Hou ,&nbsp;Babu J. Padanilam","doi":"10.1016/j.ncrna.2025.09.002","DOIUrl":"10.1016/j.ncrna.2025.09.002","url":null,"abstract":"<div><div>The increasing incidence of prostate cancer (PCa), particularly the emergence of treatment-resistant castration-resistant prostate cancer (CRPC), has intensified research efforts to address this lethal disease. Circadian rhythm gene alterations have been identified as critical factors influencing PCa progression and treatment resistance, warranting further investigation into their roles in PCa biology.</div><div>In this study, we identified a significant downregulation of <em>PER1</em> and its associated miRNA, miR-6883-5p, in PCa cells and clinical samples, suggesting their potential clinical relevance. Functional analyses demonstrated that miR-6883-5p suppresses the proliferation of enzalutamide-resistant PCa cells both in vitro and in vivo by directly targeting AR-V7. Furthermore, we delineated the regulatory functions of the transcription factors BMAL1 and CLOCK in promoting the expression of <em>PER1</em> and miR-6883-5p, while miR-6883-5p negatively regulates CLOCK expression, thereby impacting the transcription-translation feedback loop (TTFL) of circadian genes.</div><div>Collectively, these findings uncover a regulatory axis involving circadian rhythm components, miR-6883-5p, AR-V7, and PCa progression, providing new mechanistic insights into treatment resistance in CRPC and highlighting the circadian clock as a potential therapeutic target.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"16 ","pages":"Pages 21-31"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159900","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":"ncFN: a comprehensive non-coding RNA function annotation framework based on a global and heterogeneous biomolecular network","authors":"Min Long ,&nbsp;Haizhou Liu ,&nbsp;Mengqin Yuan ,&nbsp;Xu Zhou ,&nbsp;Tao Zhang ,&nbsp;Quan Wang ,&nbsp;Wei Jiang","doi":"10.1016/j.ncrna.2025.09.007","DOIUrl":"10.1016/j.ncrna.2025.09.007","url":null,"abstract":"<div><div>Increasing evidence indicates that non-coding RNAs (ncRNAs) have emerged as essential factors in most biological processes through diverse mechanisms. However, the biological functions of most ncRNAs are still poorly understood. Here, we developed ncFN, a novel and comprehensive framework for ncRNA function annotation based on a global and heterogeneous biomolecular network. Specifically, we constructed a Global Interaction Network (GIN) by integrating ncRNA-ncRNA, ncRNA-protein coding gene (PCG), and PCG-PCG interactions. The GIN consists of 565,482 edges connecting 17,060 PCGs and 12,616 ncRNAs, including 1095 microRNAs (miRNAs), 3563 long non-coding RNAs (lncRNAs), and 7958 circular RNAs (circRNAs). For each ncRNA, we quantified Association Strengths (ASs) between the ncRNA and PCGs through Random Walk with Restart in GIN. Then, Gene Set Enrichment Analysis was performed with ASs as input to annotate the function of the ncRNA. Compared to most conventional methods that only focus on a single ncRNA type, ncFN offers significant advantages in covering diverse ncRNA types and a larger number of ncRNA molecules. Moreover, we demonstrated the superiority of ncFN by comparing it with other methods in the annotation of well-acknowledged disease-relevant ncRNAs and differentially expressed ncRNAs in diseases. Finally, ncFN also facilitated enrichment analysis with multiple ncRNAs or pathways as input. In conclusion, ncFN is a comprehensive and reliable tool for functional annotation of miRNAs, lncRNAs, and circRNAs, making it highly suitable for widespread use in ncRNA research. ncFN is freely accessible at <span><span>http://www.jianglab.cn/ncFN/</span><svg><path></path></svg></span>, and all codes are deposited on GitHub (<span><span>https://github.com/LongMin0705/ncFN</span><svg><path></path></svg></span>).</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"16 ","pages":"Pages 70-78"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145326034","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":"circMRPL35 promotes gastric cancer progression through the miR-6809-3p/ZNF90 axis and affects the EMT process and TGF-β1/SMAD2/3 signaling","authors":"Xiuping Wang ,&nbsp;Zhendong Yao ,&nbsp;Yu Liu ,&nbsp;Boneng Mao ,&nbsp;Chen Shao ,&nbsp;Shihe Shao","doi":"10.1016/j.ncrna.2025.10.002","DOIUrl":"10.1016/j.ncrna.2025.10.002","url":null,"abstract":"<div><h3>Background</h3><div>Circular RNAs (circRNAs) have been implicated in developing gastric cancer (GC). However, the role of circMRPL35 in GC remains unknown.</div></div><div><h3>Methods</h3><div>This study identified differentially expressed circMRPL35 using gene expression profiles GSE78092, GSE131414, and GSE100170. RNA R enzyme and RNA FISH assays were used to explore the origin, cyclization site, and cellular localization of circMRPL35. The functions of circMRPL35, miR-6809-3p, and ZNF90 in GC cells were evaluated through loss- and gain-of-function experiments. The epithelial-mesenchymal transition (EMT) process and the TGF-β1/SMAD signaling pathway were analyzed using Western blot and immunofluorescence assays. Subcutaneous tumor models in nude mice were utilized to evaluate the impact of circMRPL35 on GC cells. The interactions among circMRPL35, miR-6809-3p, and ZNF90 were confirmed through luciferase reporter and rescue assays.</div></div><div><h3>Results</h3><div>The study demonstrated that circMRPL35, present in the cytoplasm and nucleus of MGC-803 and HGC-27 cells, originates from the cyclization of exons 4 and 5 on chromosome 2. In GC tissues and cells, circMRPL35 and ZNF90 were upregulated, while miR-6809-3p was downregulated. circMRPL35 and ZNF90 enhanced cell mobility and invasion and suppressed apoptosis by modulating the EMT process and TGF-β1/SMAD2/3 signaling pathway; conversely, miR-6809-3p exhibited the opposite effects. Mechanistically, circMRPL35 sponges miR-6809-3p to regulate ZNF90, thereby enhancing the phenotype of GC cells.</div></div><div><h3>Conclusions</h3><div>These results indicate that circMRPL35 acts as an oncogenic driver via the miR-6809-3p/ZNF90 axis, affecting the EMT process and the TGF-β1/SMAD2/3 signaling pathway to promote GC progression.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"16 ","pages":"Pages 79-92"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145418117","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 expression in prostate cancer: From in silico analysis to urinary EV-based liquid biopsy for prognosis","authors":"Simona De Summa ,&nbsp;Letizia Porcelli ,&nbsp;Giuseppe De Palma ,&nbsp;Antonio Palazzo ,&nbsp;Giuseppina Matera ,&nbsp;Alessandro Caniglia ,&nbsp;Roberta Di Fonte ,&nbsp;Rosella Fasano ,&nbsp;Francesco A. Zito ,&nbsp;Stefania Tommasi ,&nbsp;Simona Serratì ,&nbsp;Amalia Azzariti","doi":"10.1016/j.ncrna.2025.10.005","DOIUrl":"10.1016/j.ncrna.2025.10.005","url":null,"abstract":"<div><div>Prostate cancer (PCa) is the most frequently diagnosed malignancy among men and remains a leading cause of cancer-related death. Despite the widespread use of diagnostic tools such as PSA testing and Gleason scoring, these methods often fall short in accurately predicting tumor progression, highlighting the urgent need for reliable, non-invasive biomarkers to improve prognosis. In this study, we explored the potential of long non-coding RNAs (lncRNAs) as novel prognostic biomarkers for PCa. An initial <em>in silico</em> analysis of public datasets identified six lncRNAs differentially expressed in PCa tissues compared to healthy and adjacent non-tumor tissues. Of these, three were validated in a cohort of prostate cancer and benign prostatic hyperplasia (BPH) tissue samples. Notably, four lncRNAs showed expression levels that increased with higher Gleason scores, suggesting their potential as indicators of disease progression rather than early detection. To evaluate their applicability in a non-invasive setting, we assessed the expression of these lncRNAs in urinary extracellular vesicles (EVs). The results evidenced that Lnc-OPRK1-3 and lnc-SRSF6-1 are candidates as non-invasive prognostic biomarkers since they were detectable in urine and exhibited expression levels that correlate with advancing disease, specifically in the transition from Gleason score 3 + 3 to 4 + 3 and above. Their detection through urine-based liquid biopsy could support more precise patient stratification and suggest clinical decision-making. Further investigation is needed to validate their functional relevance and clinical utility.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"16 ","pages":"Pages 117-125"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466253","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":"Small RNA sequencing in individually selected sperm: Biomarkers for male subfertility and predictors of pregnancy success","authors":"Mohammad A. Al Smadi ,&nbsp;Haidar Haidar ,&nbsp;Albert Salas-Huetos ,&nbsp;Ulrike Fischer ,&nbsp;Hashim Abdul-Khaliq ,&nbsp;Eckart Meese ,&nbsp;Masood Abu-Halima","doi":"10.1016/j.ncrna.2025.09.008","DOIUrl":"10.1016/j.ncrna.2025.09.008","url":null,"abstract":"<div><h3>Background</h3><div>Sperm quality defined by motility and morphology has critical implications for fertility and pregnancy outcomes. Small RNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), play regulatory roles and may reflect underlying sperm function. This study aimed to identify small RNA types in sperm based on motility and morphology, examine their correlation with sperm and clinical parameters, and develop diagnostic tools to predict pregnancy outcomes.</div></div><div><h3>Methods</h3><div>A total of 98 male partners of couples undergoing infertility treatment were included. Thirteen males provided 39 sperm samples categorized into three groups based on quality: A (good), B (intermediate), and C (poor), each with 1500 individually selected sperm. Additionally, 85 males contributed purified sperm samples with various spermatogenic impairments. Small RNA sequencing was performed followed by RT-qPCR validation.</div></div><div><h3>Results</h3><div>Small RNA sequencing revealed a diverse RNA landscape in sperm, with long non-coding RNA (lncRNA) being the most abundant. Regulatory RNAs such as miRNAs and piRNAs were present at varying levels. Differential expression analysis identified 16 miRNAs and 37 piRNAs significantly different between groups A and C. Strong correlations were observed between miRNA/piRNA expression and sperm motility and morphology in groups A and C, but not in group B. miRNA expression levels were associated with sperm quality and pregnancy outcomes, including embryo quality, β-hCG levels, and live birth. Notably, hsa-miR-15b-5p, hsa-miR-19a-5p, and hsa-miR-20a-5p were linked to sperm impairments and hormonal markers (β-hCG, FSH, and LH). Higher expression of these miRNAs was associated with negative β-hCG outcomes and poor IVF prognosis. Lower expression of hsa-miR-15b-5p and hsa-miR-20a-5p was found in G1 embryos compared to G2 embryos. These miRNAs were also significantly correlated with live birth outcomes: higher expression was linked to failed IVF, while lower expression was linked to successful live births. Diagnostic validation showed AUCs of 0.76, 0.71, and 0.74 for hsa-miR-15b-5p, hsa-miR-19a-5p, and hsa-miR-20a-5p, respectively. A combined model yielded an AUC of 0.75.</div></div><div><h3>Conclusion</h3><div>These findings suggest that hsa-miR-15b-5p, hsa-miR-19a-5p, and hsa-miR-20a-5p could serve as potential biomarkers for assessing sperm quality and predicting pregnancy outcomes.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"16 ","pages":"Pages 126-143"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520423","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-21 modulates P.g-LPS induced apoptosis and inflammatory response in HUVECs via NF-κB/iNOS/NO pathway by targeting PDCD4","authors":"Jing Ren ,&nbsp;Huiqiong Zou ,&nbsp;Siyu Sun ,&nbsp;Shan Chen ,&nbsp;Rui He ,&nbsp;Qianbing Zhou ,&nbsp;Jun Tao ,&nbsp;Junying Yang","doi":"10.1016/j.ncrna.2025.10.001","DOIUrl":"10.1016/j.ncrna.2025.10.001","url":null,"abstract":"<div><h3>Background</h3><div><em>Porphyromonas gingivalis</em> lipopolysaccharide (<em>P.g-</em>LPS), a key virulence factor in periodontitis, contributes to systemic vascular diseases, notably atherosclerosis. MicroRNA-21 (miR-21), a critical post-transcriptional regulator, influences inflammation and vascular pathology, but its role in endothelial responses to <em>P.g-</em>LPS remains unclear.</div></div><div><h3>Methods</h3><div>Gingival biopsies from eight patients with periodontitis and eight healthy controls were analyzed using immunofluorescence co-labeling for Cluster of Differentiation 31 (CD31) with TUNEL or Interleukin-6 (IL-6) to assess endothelial apoptosis and inflammation. MiR-21 levels were quantified using quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR). Human umbilical vein endothelial cells (HUVECs) were treated with <em>P.g-</em>LPS and transfected with miR-21 mimics or inhibitors. Apoptosis, proliferation, and migration were evaluated by flow cytometry, Cell Counting Kit-8 (CCK-8) assay, and wound healing analysis, respectively. Western blotting and Enzyme-Linked Immunosorbent Assay(ELISA) measured inflammatory and apoptotic markers. Luciferase reporter assays confirmed that PDCD4 was a direct target of miR-21, and the effects of Programmed Cell Death 4(PDCD4) knockdown on Nuclear Factor kappa B (NF-κB)/Inducible Nitric Oxide Synthase (iNOS)/Nitric Oxide (NO) signaling were examined.</div></div><div><h3>Results</h3><div>Endothelial cells from patients with periodontitis exhibited increased apoptosis and inflammation. <em>P.g-</em>LPS significantly reduced miR-21 expression in HUVECs. MiR-21 inhibition exacerbated apoptosis and inflammatory mediator expression, while suppressing proliferation and migration.MiR-21 overexpression mitigated these effects. PDCD4 was validated as a direct miR-21 target. Suppression of miR-21 enhanced NF-κB/iNOS/NO activation, and PDCD4 knockdown attenuated this pathway, indicating a regulatory mechanism.</div></div><div><h3>Conclusion</h3><div>MiR-21 acts as a protective regulator against <em>P.g-</em>LPS-induced endothelial injury by targeting PDCD4 and modulating the NF-κB/iNOS/NO pathway, thereby reducing inflammation and apoptosis. These findings indicate that miR-21 is a potential therapeutic target for vascular complications associated with chronic inflammatory diseases like periodontitis.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"16 ","pages":"Pages 144-155"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520422","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}