Non-coding RNA Research最新文献

{"title":"The role of non-coding RNA regulates stem cell programmed death in disease therapy","authors":"Ziling Liao ,&nbsp;Weidong Liu ,&nbsp;Lei Wang ,&nbsp;Wen Xie ,&nbsp;Chaoyan Yao ,&nbsp;Qianping Huang ,&nbsp;Xingjun Jiang ,&nbsp;Caiping Ren","doi":"10.1016/j.ncrna.2025.04.005","DOIUrl":"10.1016/j.ncrna.2025.04.005","url":null,"abstract":"<div><div>Programmed cell death (PCD), an essential and inevitable phenomenon, is integral to organismal development. It not only maintains cellular homeostasis but also prevents aberrant cell proliferation, thereby protecting normal growth and development from detrimental factors. And it is governed by a highly complex and sophisticated regulatory network in which non-coding RNAs (ncRNAs) play pivotal roles. ncRNAs refer to RNA molecules that do not encode proteins and encompass various types, including long non-coding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA). Herein, we investigate the specific signaling mechanisms by which ncRNAs regulate stem cells, elucidating their role in modulating PCD process through interactions with specific molecules. We further summarize the impact of above modulating role on stem cell differentiation, proliferation, cycle regulation and diverse disease development and therapy. Additionally, given the emerging trends in the therapeutic application of ncRNAs and stem cells, we explore the potential of their combined application for disease treatment.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"13 ","pages":"Pages 57-70"},"PeriodicalIF":5.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894752","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 mechanism by which MALAT1/CREG1 regulates premature rupture of fetal membrane through autophagy mediated differentiation of amniotic fibroblasts","authors":"Xiaomei Huang ,&nbsp;Ting Huang ,&nbsp;Aixing Chen ,&nbsp;Yong Shao","doi":"10.1016/j.ncrna.2025.04.004","DOIUrl":"10.1016/j.ncrna.2025.04.004","url":null,"abstract":"<div><h3>Background</h3><div>Premature rupture of fetal membrane (PROM) is one of the main causes of premature delivery. The amniotic membrane plays a major role in bearing weight, and amniotic fibroblasts play an important role. The purpose of this study was to explore the scientific problems associated with amniotic membrane repair by intervening with fibroblasts to provide evidence for the clinical treatment of PROM.</div></div><div><h3>Methods</h3><div>This research group conducted experiments on fetal membrane tissue via single-cell sequencing, Sirius staining, fluorescence staining and Raman spectroscopy to explore changes in fetal membrane structure and verified key targets and pathways in clinical tissues and primary fibroblasts through WB, PCR, RNA Pulldown, RIP and molecular docking experiments.</div></div><div><h3>Results</h3><div>The fetal membrane structure in the PROM group was obviously damaged, and the amniotic fibroblasts were activated and autophagy was activated, and the activated autophagy promoted the activation of fibroblasts. The expression of Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) was significantly increased in amniotic fibroblasts. RNA PULL DOWN and molecular docking results suggested that MALAT1 binds to human E1A promoter repressor 1 (CREG1) and promotes autophagy.</div></div><div><h3>Conclusions</h3><div>By interacting with CREG1, MALAT1 can increase the expression of CREG1, regulate the expression of autophagy-related molecules, mediate the differentiation of amniotic fibroblasts into myofibroblasts, participate in amniotic repair, and promote the repair of PROM fetal membrane tissue.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"13 ","pages":"Pages 29-42"},"PeriodicalIF":5.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844245","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":"USF1-activated hsa_circ_0076691 induces oxaliplatin resistance via facilitating FGF9 expression in miR-589-3p-dependent manners","authors":"Lingyu Tang ,&nbsp;Xuan Deng ,&nbsp;Ming Guan ,&nbsp;Liang Zhong","doi":"10.1016/j.ncrna.2025.04.003","DOIUrl":"10.1016/j.ncrna.2025.04.003","url":null,"abstract":"<div><div>Chemotherapeutic efficacy in colorectal cancer (CRC) is significantly hindered by the development of drug resistance. Emerging evidence indicates that circular RNAs (circRNAs) play pivotal roles in various cancer-related biological processes. Nonetheless, the specific role of circRNAs in oxaliplatin resistance in CRC remains largely unexplored. In this study, hsa_circ_0076691 (circ76691) overexpression was observed in the oxaliplatin-resistant CRC group and could predict poor prognosis. Functional analyses revealed that circ76691 attenuates oxaliplatin-induced apoptosis both <em>in vitro</em> and <em>in vivo</em>, thereby contributing to enhanced oxaliplatin resistance. Mechanistically, circ76691 transcriptionally downregulates miR-589–3p expression and acts as a molecular sponge for miR-589–3p, sequestering it from its downstream targets. Notably, fibroblast growth factor 9 (FGF9), identified as a downstream inhibitory target of miR-589–3p, is subsequently upregulated due to circ76691 activity. Furthermore, circ76691 expression is transcriptionally induced by USF1 through direct binding to its promoter region. Collectively, these findings elucidate the USF1/circ76691/miR-589–3p/FGF9 axis in inhibiting oxaliplatin-induced apoptosis, suggesting circ76691 as a potential therapeutic target to enhance the efficacy of platinum-based therapy.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"13 ","pages":"Pages 15-28"},"PeriodicalIF":5.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143837909","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":"HNRNPC stabilizes m6A-modified AC145207.5 to accelerate tumorigenesis in colorectal cancer by impeding the Nrf2/GPX4 axis-mediated ferroptosis","authors":"Dan Liu ,&nbsp;Shanshan Lin ,&nbsp;Yueben Hu ,&nbsp;Jianyong Xiong ,&nbsp;Hongtao Wan ,&nbsp;Yanglin Chen ,&nbsp;Taohui Ding ,&nbsp;Hu Zhao ,&nbsp;Renjie Jiang ,&nbsp;Zhijiang Huang ,&nbsp;Dengke Yao ,&nbsp;Ming Li ,&nbsp;Xiaojian Zhu ,&nbsp;Bo Yi","doi":"10.1016/j.ncrna.2025.04.002","DOIUrl":"10.1016/j.ncrna.2025.04.002","url":null,"abstract":"<div><div>Ferroptosis is an apoptosis-independent cell death pathway characterized by heightened lipid peroxidation, which shows promise for tumor suppression. Despite extensive research on long non-coding RNAs (LncRNAs) in ferroptosis, their role in colorectal cancer (CRC) remains underexplored. We investigated the upregulation of AC145207.5 and HNRNPC expression in CRC tissues through public dataset analysis and in-house validation, identifying them as having significant diagnostic potential. <em>In vitro</em> experiments including MTS assay, transwell, and colony formation, alongside <em>in vivo</em> studies using xenograft models, elucidated the synergistic carcinogenic role of the HNRNPC/AC145207.5 axis in promoting the malignant characteristics of CRC. Mechanistically, the m6A reader HNRNPC stabilized m6A-modified AC145207.5, contributing to its stabilization and upregulation. Consequently, AC145207.5 activated the Nrf2/GPX4 axis, resulting in increased GPX4 expression, inhibition of GPX4-mediated ferroptosis, and facilitation of CRC progression. Our findings underscore the clinical relevance of the HNRNPC/AC145207.5 axis in CRC and illuminate its regulatory role in ferroptosis, suggesting implications for targeted precision medicine in CRC.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"13 ","pages":"Pages 43-56"},"PeriodicalIF":5.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847595","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":"LINC02679 regulates TRIML2 to promote gastric cancer proliferation and invasion via targeting miR-5004-3p","authors":"Yingying Wang ,&nbsp;Wenbo Liu ,&nbsp;Xiaohan Zhao ,&nbsp;Yong Li ,&nbsp;Chao Song ,&nbsp;Bingjie Huo ,&nbsp;Yanru Song ,&nbsp;Bibo Tan","doi":"10.1016/j.ncrna.2025.04.001","DOIUrl":"10.1016/j.ncrna.2025.04.001","url":null,"abstract":"<div><div>As a key protein, Tripartite motif family-like 2 (TRIML2) is crucial to the p53-mediated apoptosis and is correlated with tumorigenesis. Emerging evidence showed that long non-coding RNAs (lncRNAs) play roles in the malignant progression of gastric cancer (GC). However, the function and underlying mechanism of LINC02679 in GC are still unclear. In this study, we detected the differentially expressed lncRNA, LINC02679, which was associated with the progression of GC. Herein, we showed that LINC02679 was overexpressed in GC tissues and correlated with poor prognosis, which aggravated GC proliferation, migration, and invasion. Mechanistically, LINC02679 sponged miR-5004-3p to promote the expression of TRIML2, regulating GC tumorigenesis and progression. Moreover, TRIML2 affected the proliferation, migration, and invasion of GC cells through TGF-β1/Smads signaling pathway. Overall, our findings proved a new mechanism and provided a promising strategy for precise therapy of GC by targeting LINC02679.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"13 ","pages":"Pages 1-14"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143820849","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":"Long non-coding RNA ANRIL/p65 negative feedback loop protects intestinal barrier function in inflammatory bowel disease","authors":"Keqi Yu ,&nbsp;Hong Peng ,&nbsp;Zhechuan Zhang ,&nbsp;Lu Ye ,&nbsp;Ke Zhan ,&nbsp;Chuanfei Li ,&nbsp;Li Gan ,&nbsp;Yuru Lin ,&nbsp;Yanhui Wang ,&nbsp;Ya Song ,&nbsp;Zhechuan Mei ,&nbsp;Shengtao Liao ,&nbsp;Jinjun Guo ,&nbsp;Lin Lv","doi":"10.1016/j.ncrna.2025.03.002","DOIUrl":"10.1016/j.ncrna.2025.03.002","url":null,"abstract":"<div><div>Patients with inflammatory bowel disease (IBD) demonstrate varying expression levels of long non-coding RNAs (lncRNAs) in their intestinal mucosa, which can potentially impact the function of the intestinal barrier. This impact may occur through the modulation of epithelial cell apoptosis, alteration of intestinal mucosal barrier permeability, and enhancement of inflammatory responses. The objective of this study was to explore the role and underlying mechanisms of the downregulated lncRNA ANRIL in modulating intestinal barrier function in IBD. Notably, ANRIL was found to be significantly downregulated in patients diagnosed with ulcerative colitis (UC), correlating strongly with disease progression. The overexpression of ANRIL in mice treated with dextran sulfate sodium (DSS) resulted in a significant reduction in colonic damage. This was accompanied by the suppression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β, and an improvement in intestinal barrier function. Transcriptome sequencing following overexpression of ANRIL revealed a significant enrichment of the NF-κB signaling pathway. In both DSS-induced mouse colitis and LPS-induced FHC cell models, the upregulation of ANRIL effectively suppressed the activation of the NF-κB pathway. Furthermore, our findings demonstrated that ANRIL competes with YY1 for binding, thereby inhibiting the interaction between YY1 and p65 subunit of NF-κB. This disruption in interaction results in the suppression of transcriptional activation of NF-κB p65, leading to a reduced expression of inflammatory cytokines and the promotion of intestinal barrier function in IBD.Additionally, we identified a negative feedback loop involving ANRIL and p65, wherein p65 binds to the ANRIL promoter, promoting ANRIL expression. In summary, the ANRIL/p65 negative feedback loop represents a potential therapeutic target for protecting intestinal barrier function in IBD.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"12 ","pages":"Pages 167-179"},"PeriodicalIF":5.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles derived microRNAs as non-invasive markers of liver fibrosis in chronically infected HCV patients: a pilot study","authors":"Victoria Cairoli ,&nbsp;Daniel Valle-Millares ,&nbsp;Pablo Ryan ,&nbsp;Lourdes Dominguez ,&nbsp;Luz Martín-Carbonero ,&nbsp;Ignacio De los Santos ,&nbsp;Elena De Matteo ,&nbsp;Beatriz Ameigeiras ,&nbsp;Marcela De Sousa ,&nbsp;Verónica Briz ,&nbsp;María V. Preciado ,&nbsp;Amanda Fernández-Rodriguez ,&nbsp;Pamela Valva","doi":"10.1016/j.ncrna.2025.03.004","DOIUrl":"10.1016/j.ncrna.2025.03.004","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Extracellular vesicles (EVs) are an increasingly promising tool for liquid biopsy in liver diseases. Hepatitis C Virus (HCV) infection, alone or together with Human Immunodeficiency Virus (HIV) infection significantly impacts on the microRNA (miRNA) EVs content resembling chronic hepatitis C (CHC) progression. The objective of the study was to delve into the intricate EVs-miRNA profiles in CHC patients with different liver fibrosis stages, aiming to pinpoint non-invasive markers capable of distinguishing significant fibrosis.&lt;/div&gt;&lt;div&gt;Plasma EV-miRNAs from 50 CHC patients (HCV+ and HCV+/HIV+) stratified in no significant (F &lt; 2) and significant (F ≥ 2) fibrosis, were massively sequenced. General linear models (GLM) were used to identify significantly differential expressed (SDE) miRNAs according to liver fibrosis stages (F ≥ 2 and F &lt; 2). Dysregulated biological pathways were subsequently analyzed &lt;em&gt;in silico&lt;/em&gt; for the following groups: i) all patients; ii) HCV+; and iii) HCV+/HIV+. Multiple-ordered logistic regression analysis was performed to develop a score to identify F ≥ 2 cases. The diagnostic potential of both the SDE miRNAs and the developed score was assessed using ROC curve analysis.&lt;/div&gt;&lt;div&gt;With respect to all CHC patients, two SDE miRNAs (hsa-miR-122-5p and hsa-miR-92a-3p) were identified which regulate genes related to cytoskeleton organization. Regarding their diagnostic performance to discriminate F ≥ 2, both miRNAs individually demonstrated acceptable diagnostic values. However, their combined use in a new score enhanced their diagnostic performance (AUROC = 0.833).&lt;/div&gt;&lt;div&gt;In the HCV+ subgroup, 8 SDE miRNAs (hsa-miR-122-5p, hsa-miR-320c, hsa-miR-3615, hsa-miR-320a-3p, hsa-miR-374b-5p, hsa-let-7a-3p, hsa-miR-199a-5p, hsa-miR-142-5p), which regulate macrophage activity and cell growth/death regulation, were recognized. Among them, hsa-miR-3615 displayed the highest diagnostic performance to discriminate F ≥ 2 (AUROC = 0.936).&lt;/div&gt;&lt;div&gt;With respect to HCV+/HIV+, 18 SDE miRNAs (hsa-miR-4508, hsa-miR-122-5p, hsa-miR-451a, hsa-miR-1290, hsa-miR-1246, hsa-miR-107, hsa-miR-15b-5p, hsa-miR-194-5p, hsa-miR-22-5p, hsa-miR-20b-5p, hsa-miR-142-5p, hsa-miR-328-3p, hsa-miR-335-3p, hsa-miR-125a-5p, hsa-miR-423-3p, hsa-let-7d-3p, hsa-miR-128-3p, hsa-miR-10a-5p) were recognized that regulate RNA silencing processes. In this case, hsa-miR-423-3p and hsa-miR-128-3p showed outstanding diagnostic performances (AUROC &gt; 0.900).&lt;/div&gt;&lt;div&gt;Distinct EVs-miRNA profiles were identified in patients with varying liver fibrosis stages, both in the overall CHC cohort and within HCV+ and HCV+/HIV+ subgroups. These specific miRNA signatures would allow the elucidation of potential mechanisms involved in clinical evolution and identification of specific biomarkers of unfavorable progression, plausible to be used in a diagnostic panel. Furthermore, the developed score demonstrates the ability to discriminate within the CHC group those i","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"12 ","pages":"Pages 132-140"},"PeriodicalIF":5.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-coding RNA-mediated granulosa cell dysfunction during ovarian aging: From mechanisms to potential interventions","authors":"Li Dong ,&nbsp;Haicui Wu ,&nbsp;Fanghua Qi ,&nbsp;Yuan Xu ,&nbsp;Wen Chen ,&nbsp;Yuqi Wang ,&nbsp;Pingping Cai","doi":"10.1016/j.ncrna.2025.03.001","DOIUrl":"10.1016/j.ncrna.2025.03.001","url":null,"abstract":"<div><div>As the earliest aging organ in the reproductive system, the ovary has both reproductive and endocrine functions, which are closely related to overall female health. The exact pathogenesis of ovarian aging (OA) remains incompletely understood, with granulosa cells (GCs) dysfunction playing a significant role in this process. Recent advancements in research and biotechnology have highlighted the importance of non-coding RNAs (ncRNAs), including micro RNAs, long non-coding RNAs, and circular RNAs, in regulating the biological functions of GCs through gene expression modulation. This paper provides a comprehensive overview of the role of ncRNAs in various cellular functions such as apoptosis, autophagy, proliferation, and steroid synthesis in GCs, and explores the underlying regulatory mechanisms. Additionally, the therapeutic potential of ncRNAs, particularly those carried by exosomes derived from mesenchymal stem cells, in delaying OA is discussed. Understanding the regulatory mechanisms of ncRNAs in GC function and the current progress in this field is crucial for identifying effective biomarkers and therapeutic targets, ultimately aiding in the early diagnosis, prognostic assessment, and individualized treatment of OA.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"12 ","pages":"Pages 102-115"},"PeriodicalIF":5.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a microRNA-Based age estimation model using whole-blood microRNA expression profiling","authors":"Yanfang Lu ,&nbsp;Anqi Chen ,&nbsp;Mengxiao Liao ,&nbsp;Ruiyang Tao ,&nbsp;Shubo Wen ,&nbsp;Suhua Zhang ,&nbsp;Chengtao Li","doi":"10.1016/j.ncrna.2025.03.003","DOIUrl":"10.1016/j.ncrna.2025.03.003","url":null,"abstract":"<div><div>Age estimation is a critical aspect of human identification. Traditional methods, reliant on morphological examinations, are often suitable for living subjects. However, there are relatively few studies on age estimation based on biological samples, such as blood. Recent advancements have concentrated on DNA methylation for forensic age prediction. However, to explore further possibilities, this study investigated microRNAs (miRNAs) as alternative molecular markers for age estimation. Peripheral blood samples from 127 healthy individuals were analyzed for miRNA expression using small RNA sequencing. Lasso regression selected 103 candidate miRNAs, and Shapley additive explanations (SHAP) analysis identified 38 key miRNAs significant for age prediction. Five machine learning models were developed, with the elastic net model achieving the best performance (MAE of 4.08 years) on the testing set, surpassing current miRNA age estimation results. Additionally, we observed significant changes in the expression levels of miRNAs in healthy individuals aged 48–52 years. This study demonstrated the potential of blood miRNA biomarkers in age prediction and provides a set of miRNA markers for developing more accurate age prediction methods.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"12 ","pages":"Pages 81-91"},"PeriodicalIF":5.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long noncoding RNA hottip maintained skeletal homeostasis via suppressing the enhancer of zeste homolog 2 (Ezh2)/histone methylation regulatory axis","authors":"Zhi-Peng Li ,&nbsp;Yong-Xin Mai ,&nbsp;Shu-Ting Zhou ,&nbsp;Chuan-jian Shi ,&nbsp;Jiang Shao ,&nbsp;Pu-ping Liang ,&nbsp;Wei-cheng Liang ,&nbsp;Jin-fang Zhang","doi":"10.1016/j.ncrna.2025.01.003","DOIUrl":"10.1016/j.ncrna.2025.01.003","url":null,"abstract":"<div><h3>Objective</h3><div>Recent evidence underscores the pivotal role of long noncoding RNAs (lncRNAs) in orchestrating bone remodeling and skeletal homeostasis by harmonizing osteoblast and osteoclast development. Notably, the oncogenic lncRNA, Hottip, implicated in osteogenesis regulation, remains insufficiently elucidated. This study aims to delineate Hottip's role in bone remodeling and skeletal homeostasis.</div></div><div><h3>Methods</h3><div>Hottip knockout mice were generated to discern its impact on bone metabolism. <em>In vitro</em> experiments probed cellular mechanisms influenced by Hottip, while molecular interactions were explored to understand its basis. The therapeutic potential of Hottip overexpression was investigated through <em>in vivo</em> experiments.</div></div><div><h3>Results</h3><div>Hottip knockout mice displayed disrupted bone metabolism, aberrant tissue, and compromised quality, leading to delayed fracture healing. <em>In vitro</em>, Hottip knockdown impeded osteoblast differentiation, while promoting osteoclast differentiation, with converse effects upon Hottip overexpression. Mechanistically, Hottip physically interacted with EZH2, inducing its degradation and enhancing osteogenic gene transcription by suppressing H3K9me3 and H3K27me3. <em>In vivo</em> experiments validated Hottip overexpression's potential to promote bone regeneration and hasten fracture healing.</div></div><div><h3>Conclusion</h3><div>In summary, this study identifies Hottip as a critical regulator in osteoblast and osteoclast differentiation, crucial for maintaining skeletal homeostasis. Hottip emerges as a promising therapeutic target for enhancing bone regeneration. These findings contribute valuable insights into lncRNA-mediated mechanisms governing skeletal dynamics<strong>.</strong></div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"12 ","pages":"Pages 141-151"},"PeriodicalIF":5.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}