Pub Date : 2026-01-24DOI: 10.1016/j.ncrna.2026.01.008
Wenhua Jiang , Yuetong Li , Zhenxiong Liu , Heng Ma , Haiyan Wang
Cardiovascular diseases (CVDs) represent the predominant global health burden, where dysregulated programmed cell death (PCD) mechanisms critically drive myocardial injury pathogenesis. Circular RNAs (circRNAs), characterized by covalently closed structures conferring high stability, function as pivotal regulators coordinating cardiomyocyte fate through integrated networks encompassing ferroptosis, apoptosis, pyroptosis, autophagy, and necroptosis. This review synthesizes advances in understanding circRNA-mediated PCD modulation via molecular sponging, protein interactions, and epigenetic regulation. Key insights establish context-dependent circRNA functionality and validate circRNA-based diagnostic panels for CVDs stratification with enhanced accuracy. Therapeutically, viral vector-delivered protective circRNAs demonstrate significant efficacy in ameliorating post-infarction apoptosis and improving cardiac function. We further evaluate emerging CRISPR-based editing technologies and nanoplatform delivery systems for clinical translation, positioning circRNA networks as promising theranostic targets while highlighting unresolved questions regarding pathway crosstalk and tissue-specific delivery.
{"title":"CircRNA-regulated programmed cell death networks in cardiomyocytes: Molecular crosstalk and therapeutic translation","authors":"Wenhua Jiang , Yuetong Li , Zhenxiong Liu , Heng Ma , Haiyan Wang","doi":"10.1016/j.ncrna.2026.01.008","DOIUrl":"10.1016/j.ncrna.2026.01.008","url":null,"abstract":"<div><div>Cardiovascular diseases (CVDs) represent the predominant global health burden, where dysregulated programmed cell death (PCD) mechanisms critically drive myocardial injury pathogenesis. Circular RNAs (circRNAs), characterized by covalently closed structures conferring high stability, function as pivotal regulators coordinating cardiomyocyte fate through integrated networks encompassing ferroptosis, apoptosis, pyroptosis, autophagy, and necroptosis. This review synthesizes advances in understanding circRNA-mediated PCD modulation via molecular sponging, protein interactions, and epigenetic regulation. Key insights establish context-dependent circRNA functionality and validate circRNA-based diagnostic panels for CVDs stratification with enhanced accuracy. Therapeutically, viral vector-delivered protective circRNAs demonstrate significant efficacy in ameliorating post-infarction apoptosis and improving cardiac function. We further evaluate emerging CRISPR-based editing technologies and nanoplatform delivery systems for clinical translation, positioning circRNA networks as promising theranostic targets while highlighting unresolved questions regarding pathway crosstalk and tissue-specific delivery.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"18 ","pages":"Pages 52-64"},"PeriodicalIF":4.7,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039816","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}
Pub Date : 2026-01-24DOI: 10.1016/j.ncrna.2026.01.009
Lang Xia , Jing Cai , Xueqin Zeng , Qian Shu , Qiong Hu , Shanshan Rao , Jing Han , Weijia Liu
Background
Idiopathic pulmonary fibrosis (IPF) is a type of interstitial lung disease that is critically influenced by epigenetic regulation and mitochondrial function during its pathogenesis and progression. Flavonoids possess significant anti-inflammatory and antioxidant properties, and among these compounds, quercetin has been shown to inhibit the progression of pulmonary fibrosis by modulating the expression of specific microRNAs (miRNAs) and alleviating oxidative stress associated with mitochondrial dysfunction. However, the precise underlying mechanism remains unclear.
Methods
We established a murine model of pulmonary fibrosis via endotracheal nebulization with bleomycin, which resulted in uniformly distributed, severe fibrotic lesions in the lungs. Quercetin (Que) was administered via the intratracheal route, enabling targeted pulmonary delivery, reducing the required drug concentration, increasing bioavailability, and minimizing potential systemic toxicity. For the assessment of histopathological changes and collagen deposition in lung tissues, we used hematoxylin–eosin (H&E) and Masson's trichrome staining. In cell experiments, we stimulated A549 cells with transforming growth factor-β1 (TGF-β1) and transfected them with a miR-423–5p inhibitor to examine the expression levels of extracellular matrix (ECM) related proteins and the NDUFS7 subunit of mitochondrial complex I. Furthermore, we evaluated mitochondrial function by measuring reactive oxygen species (ROS) production, adenosine triphosphate (ATP) content, hydrogen peroxide (H2O2) levels, and the mitochondrial membrane potential.
Results
Our research revealed that quercetin regulated the level of miR-423–5p in mouse lung tissue, as well as the expression of the mitochondrial complex I subunit NDUFS7. After 15 days of endotracheal nebulization with quercetin, extracellular matrix remodeling and collagen deposition in mouse lung tissue were alleviated, and the pulmonary fibrosis induced by bleomycin was improved. In vitro experiments demonstrated that inhibiting miR-423–5p enabled the normal translation and expression of NDUFS7, and improves mitochondrial function, ultimately alleviating the ECM remodeling induced by TGF-β1.
Conclusion
Targeting miR-423–5p to modulate NDUFS7 expression represents a potential therapeutic strategy for ameliorating mitochondrial dysfunction and suppressing pulmonary fibrosis.
{"title":"miR-423–5p/NDUFS7-mediated mitochondrial function modulation contributes to quercetin-induced attenuation of pulmonary fibrosis via extracellular matrix remodeling regulation","authors":"Lang Xia , Jing Cai , Xueqin Zeng , Qian Shu , Qiong Hu , Shanshan Rao , Jing Han , Weijia Liu","doi":"10.1016/j.ncrna.2026.01.009","DOIUrl":"10.1016/j.ncrna.2026.01.009","url":null,"abstract":"<div><h3>Background</h3><div>Idiopathic pulmonary fibrosis (IPF) is a type of interstitial lung disease that is critically influenced by epigenetic regulation and mitochondrial function during its pathogenesis and progression. Flavonoids possess significant anti-inflammatory and antioxidant properties, and among these compounds, quercetin has been shown to inhibit the progression of pulmonary fibrosis by modulating the expression of specific microRNAs (miRNAs) and alleviating oxidative stress associated with mitochondrial dysfunction. However, the precise underlying mechanism remains unclear.</div></div><div><h3>Methods</h3><div>We established a murine model of pulmonary fibrosis via endotracheal nebulization with bleomycin, which resulted in uniformly distributed, severe fibrotic lesions in the lungs. Quercetin (Que) was administered via the intratracheal route, enabling targeted pulmonary delivery, reducing the required drug concentration, increasing bioavailability, and minimizing potential systemic toxicity. For the assessment of histopathological changes and collagen deposition in lung tissues, we used hematoxylin–eosin (H&E) and Masson's trichrome staining. In cell experiments, we stimulated A549 cells with transforming growth factor-β1 (TGF-β1) and transfected them with a miR-423–5p inhibitor to examine the expression levels of extracellular matrix (ECM) related proteins and the NDUFS7 subunit of mitochondrial complex I. Furthermore, we evaluated mitochondrial function by measuring reactive oxygen species (ROS) production, adenosine triphosphate (ATP) content, hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) levels, and the mitochondrial membrane potential.</div></div><div><h3>Results</h3><div>Our research revealed that quercetin regulated the level of miR-423–5p in mouse lung tissue, as well as the expression of the mitochondrial complex I subunit NDUFS7. After 15 days of endotracheal nebulization with quercetin, extracellular matrix remodeling and collagen deposition in mouse lung tissue were alleviated, and the pulmonary fibrosis induced by bleomycin was improved. In vitro experiments demonstrated that inhibiting miR-423–5p enabled the normal translation and expression of NDUFS7, and improves mitochondrial function, ultimately alleviating the ECM remodeling induced by TGF-β1.</div></div><div><h3>Conclusion</h3><div>Targeting miR-423–5p to modulate NDUFS7 expression represents a potential therapeutic strategy for ameliorating mitochondrial dysfunction and suppressing pulmonary fibrosis.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"18 ","pages":"Pages 65-76"},"PeriodicalIF":4.7,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039438","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}
Pub Date : 2026-01-24DOI: 10.1016/j.ncrna.2026.01.001
Qianqi Xiong , Ziyang Zhang , Yiping Bai , Li Liu , Yue Zhang , Jing Jia , Yingying Zhang
Ventilator-induced lung injury (VILI) is characterized by pathological features such as infiltration of inflammatory cells, increased alveolar permeability, and changes in lung compliance. The underlying mechanisms responsible for these manifestations during mechanical ventilation remain unclear. Low tidal volume ventilation and positive end-expiratory pressure (PEEP) can mitigate pulmonary edema and improve lung compliance. However, these strategies do not fully prevent VILI, and mortality remains high. Non-coding RNAs (ncRNAs) are involved in mechanotransduction processes during ventilation by modulating cellular functions through the activation of inflammatory signaling pathways, such as Toll-like receptor (TLR), Janus kinase/signal transducer and activator of transcription (JAK-STAT), and nuclear factor kappa-B (NF-κB). These pathways contribute to the development of VILI and possess notable diagnostic, differential diagnostic, and therapeutic potential. This review offers a comprehensive evaluation of current research on microRNAs and long non-coding RNAs in relevant models of VILI.
呼吸机诱导的肺损伤(VILI)以炎症细胞浸润、肺泡通透性增加、肺顺应性改变等病理特征为特征。机械通气期间这些表现的潜在机制尚不清楚。低潮气量通气和呼气末正压通气(PEEP)可减轻肺水肿,改善肺顺应性。然而,这些策略并不能完全预防VILI,死亡率仍然很高。非编码rna (ncRNAs)通过激活炎症信号通路,如toll样受体(TLR)、Janus激酶/信号转导和转录激活因子(JAK-STAT)和核因子κ b (NF-κB),调节细胞功能,参与通气过程中的机械转导过程。这些途径有助于VILI的发展,并具有显著的诊断、鉴别诊断和治疗潜力。本文对VILI相关模型中microrna和长链非编码rna的研究现状进行了综述。
{"title":"The emerging regulatory roles of non-coding RNA in Ventilator-induced Lung Injury","authors":"Qianqi Xiong , Ziyang Zhang , Yiping Bai , Li Liu , Yue Zhang , Jing Jia , Yingying Zhang","doi":"10.1016/j.ncrna.2026.01.001","DOIUrl":"10.1016/j.ncrna.2026.01.001","url":null,"abstract":"<div><div>Ventilator-induced lung injury (VILI) is characterized by pathological features such as infiltration of inflammatory cells, increased alveolar permeability, and changes in lung compliance. The underlying mechanisms responsible for these manifestations during mechanical ventilation remain unclear. Low tidal volume ventilation and positive end-expiratory pressure (PEEP) can mitigate pulmonary edema and improve lung compliance. However, these strategies do not fully prevent VILI, and mortality remains high. Non-coding RNAs (ncRNAs) are involved in mechanotransduction processes during ventilation by modulating cellular functions through the activation of inflammatory signaling pathways, such as Toll-like receptor (TLR), Janus kinase/signal transducer and activator of transcription (JAK-STAT), and nuclear factor kappa-B (NF-κB). These pathways contribute to the development of VILI and possess notable diagnostic, differential diagnostic, and therapeutic potential. This review offers a comprehensive evaluation of current research on microRNAs and long non-coding RNAs in relevant models of VILI.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"18 ","pages":"Pages 77-86"},"PeriodicalIF":4.7,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039439","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}
Pub Date : 2026-01-22DOI: 10.1016/j.ncrna.2026.01.005
{"title":"List of reviewers in 2025","authors":"","doi":"10.1016/j.ncrna.2026.01.005","DOIUrl":"10.1016/j.ncrna.2026.01.005","url":null,"abstract":"","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"16 ","pages":"Pages 178-180"},"PeriodicalIF":4.7,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022445","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}
Pub Date : 2026-01-22DOI: 10.1016/j.ncrna.2025.12.005
Chaimae Baiddou , Mehdi Knidiri , Bouchra Ghazi , Asmaa Abu Obaid , Salsabil Hamdi , Khaoula Errafii
Circular RNAs (circRNAs), a subtype of RNA molecules, possess distinctive characteristics, including their closed circular structure, stability, tissue specificity and long half-life compared to their linear counterparts. Initially presumed to be non-functional byproducts of splicing, advances in RNA-seq and bioinformatics have revealed the existence of these RNAs and begun to clarify their functions. Insight into their diverse functions revealed their roles, including regulating various cellular processes such as gene expression, transcription, translation into proteins (e.g., cap-independent translation), binding to microRNAs (miRNAs), and interacting with proteins. Moreover, mitochondria-encoded circular RNAs (mecciRNAs) have emerged as a novel subclass of circRNAs. Notably circRNAs have been associated with the development or progression of diseases (e.g., cancer, cardiometabolic and neurodegenerative disorders), highlighting diagnostic and therapeutic potential. In our review, we aim to summarize the current knowledge on circRNAs, covering their biogenesis, functions, identification tools, and potential biomedical applications.
{"title":"The circular RNA landscape: Biogenesis, functions, identification pipelines, and biomedical applications","authors":"Chaimae Baiddou , Mehdi Knidiri , Bouchra Ghazi , Asmaa Abu Obaid , Salsabil Hamdi , Khaoula Errafii","doi":"10.1016/j.ncrna.2025.12.005","DOIUrl":"10.1016/j.ncrna.2025.12.005","url":null,"abstract":"<div><div>Circular RNAs (circRNAs), a subtype of RNA molecules, possess distinctive characteristics, including their closed circular structure, stability, tissue specificity and long half-life compared to their linear counterparts. Initially presumed to be non-functional byproducts of splicing, advances in RNA-seq and bioinformatics have revealed the existence of these RNAs and begun to clarify their functions. Insight into their diverse functions revealed their roles, including regulating various cellular processes such as gene expression, transcription, translation into proteins (e.g., cap-independent translation), binding to microRNAs (miRNAs), and interacting with proteins. Moreover, mitochondria-encoded circular RNAs (mecciRNAs) have emerged as a novel subclass of circRNAs. Notably circRNAs have been associated with the development or progression of diseases (e.g., cancer, cardiometabolic and neurodegenerative disorders), highlighting diagnostic and therapeutic potential. In our review, we aim to summarize the current knowledge on circRNAs, covering their biogenesis, functions, identification tools, and potential biomedical applications.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"18 ","pages":"Pages 39-51"},"PeriodicalIF":4.7,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039440","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}
Pub Date : 2026-01-19DOI: 10.1016/j.ncrna.2026.01.002
Rambaldelli G. , Asghar S. , Venturi G. , Zacchini F. , Serra M. , Giovannini C. , Gramantieri L. , Bernini M. , Inga A. , Dassi E. , Montanaro L.
{"title":"Corrigendum to < ‘Characterization of small nucleolar RNA retaining transcripts in human normal and cancer cells’> <[Non-coding RNA Research vol. 13 (2025) 153–161]>","authors":"Rambaldelli G. , Asghar S. , Venturi G. , Zacchini F. , Serra M. , Giovannini C. , Gramantieri L. , Bernini M. , Inga A. , Dassi E. , Montanaro L.","doi":"10.1016/j.ncrna.2026.01.002","DOIUrl":"10.1016/j.ncrna.2026.01.002","url":null,"abstract":"","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"17 ","pages":"Page 160"},"PeriodicalIF":4.7,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038054","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}
Pub Date : 2026-01-17DOI: 10.1016/j.ncrna.2025.12.003
Maryam Pirhoushiaran , Kamilah Walker-Charles , Tsung-Hung Yao , Satwikreddy Putluri , Nehal Patel , Daniel H. Wang , Isabel Wang , Srividya Arjuna , Antonio Dono , Angel Bueno , Sophia Nguyen , Ashish P. Balar , Jason T. Huse , Suprateek Kundu , Yoshua Esquenazi , Chirag B. Patel , Sujit S. Prabhu , Frederick F. Lang , Leomar Y. Ballester
Mutations in isocitrate dehydrogenase (IDH) genes, specifically IDH1 and IDH2, are frequently observed in diffuse gliomas (DG) and define distinct molecular subtypes, namely IDH-wildtype and IDH-mutant. Abnormal expression of extracellular vesicle-derived microRNAs (EV-miRNAs) in the cerebrospinal fluid (CSF) of DG patients may serve as minimally invasive diagnostic and prognostic biomarkers. To investigate this potential, we employed miRNA-sequencing (miRNA-seq), quantitative real-time PCR (qRT-PCR), and multivariable logistic regression (MLR) to identify differentially expressed microRNAs (DE-miRNAs) in CSF samples from DG patients. qRT-PCR analysis demonstrated that EV-miR-21-5p effectively differentiated CSF from glioblastoma (GBM) patients versus controls (p = 0.012, AUC = 0.84) and IDH-mutant gliomas versus controls (p = 0.003, AUC = 0.93). MLR identified five miRNAs (miR-150-5p, miR-142-3p, miR-19b-3p, miR-99a-5p, and miR-27b-3p) that accurately distinguished IDH-wildtype from IDH-mutant gliomas (AUC = 1.00), while GBM CSF was reliably separated from controls (AUC = 1.00) based on significantly reduced levels of nine miRNAs, including miR-1298-5p, miR-1911-5p, miR-195-5p, miR-196a-5p, miR-26a-5p, miR-26b-5p, miR-30a-3p, miR-30a-5p, and miR-30e-5p. Notably, miR-142-3p alone achieved complete discrimination of IDH-mutant gliomas from controls (AUC = 1.00). Ingenuity Pathway Analysis (IPA) revealed that miR-16-5p and other miRNAs with seed AGCAGCA formed the largest interaction network in GBM, while disease enrichment analysis using Database for Annotation, Visualization, and Integrated Discovery (DAVID) confirmed that the 1000 predicted mRNA targets of DE-miRNAs in GBM were disease relevant. Collectively, these findings identify a robust panel of CSF-derived miRNAs capable of distinguishing IDH-mutant gliomas, GBM, and non-tumor states, supporting the potential of EV-miRNAs as minimally invasive biomarkers for the molecular characterization of diffuse gliomas.
{"title":"Exploring CSF microRNA signatures as diagnostic biomarkers in adult-type diffuse gliomas","authors":"Maryam Pirhoushiaran , Kamilah Walker-Charles , Tsung-Hung Yao , Satwikreddy Putluri , Nehal Patel , Daniel H. Wang , Isabel Wang , Srividya Arjuna , Antonio Dono , Angel Bueno , Sophia Nguyen , Ashish P. Balar , Jason T. Huse , Suprateek Kundu , Yoshua Esquenazi , Chirag B. Patel , Sujit S. Prabhu , Frederick F. Lang , Leomar Y. Ballester","doi":"10.1016/j.ncrna.2025.12.003","DOIUrl":"10.1016/j.ncrna.2025.12.003","url":null,"abstract":"<div><div>Mutations in isocitrate dehydrogenase (IDH) genes, specifically IDH1 and IDH2, are frequently observed in diffuse gliomas (DG) and define distinct molecular subtypes, namely IDH-wildtype and IDH-mutant. Abnormal expression of extracellular vesicle-derived microRNAs (EV-miRNAs) in the cerebrospinal fluid (CSF) of DG patients may serve as minimally invasive diagnostic and prognostic biomarkers. To investigate this potential, we employed miRNA-sequencing (miRNA-seq), quantitative real-time PCR (qRT-PCR), and multivariable logistic regression (MLR) to identify differentially expressed microRNAs (DE-miRNAs) in CSF samples from DG patients. qRT-PCR analysis demonstrated that EV-miR-21-5p effectively differentiated CSF from glioblastoma (GBM) patients versus controls (p = 0.012, AUC = 0.84) and IDH-mutant gliomas versus controls (p = 0.003, AUC = 0.93). MLR identified five miRNAs (miR-150-5p, miR-142-3p, miR-19b-3p, miR-99a-5p, and miR-27b-3p) that accurately distinguished IDH-wildtype from IDH-mutant gliomas (AUC = 1.00), while GBM CSF was reliably separated from controls (AUC = 1.00) based on significantly reduced levels of nine miRNAs, including miR-1298-5p, miR-1911-5p, miR-195-5p, miR-196a-5p, miR-26a-5p, miR-26b-5p, miR-30a-3p, miR-30a-5p, and miR-30e-5p. Notably, miR-142-3p alone achieved complete discrimination of IDH-mutant gliomas from controls (AUC = 1.00). Ingenuity Pathway Analysis (IPA) revealed that miR-16-5p and other miRNAs with seed AGCAGCA formed the largest interaction network in GBM, while disease enrichment analysis using Database for Annotation, Visualization, and Integrated Discovery (DAVID) confirmed that the 1000 predicted mRNA targets of DE-miRNAs in GBM were disease relevant. Collectively, these findings identify a robust panel of CSF-derived miRNAs capable of distinguishing IDH-mutant gliomas, GBM, and non-tumor states, supporting the potential of EV-miRNAs as minimally invasive biomarkers for the molecular characterization of diffuse gliomas.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"18 ","pages":"Pages 22-38"},"PeriodicalIF":4.7,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039437","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}
Liquid-liquid phase separation (LLPS) is a biophysical mechanism by which certain biomolecules demix from the cytosol or nucleoplasm to form membraneless organelles. These droplet-like assemblies are dynamic and reversible, allowing selective enrichment of specific proteins and nucleic acids while excluding others. Classical examples include the nucleolus, P-bodies, and stress granules, all of which exhibit liquid-like behaviors such as rapid fusion, fission, and molecular exchange. Most importantly, the LLPS property has been implicated with a plethora of physiological and pathological processes. Historically, research on LLPS focused on protein drivers, especially RNA-binding proteins (RBPs) with low complexity domains or intrinsically disordered regions, contributing to multivalent weak interactions. However, it is now clear that RNA molecules especially noncoding RNAs are integral components and often active modulators of these condensates. Noncoding RNAs, including long noncoding RNAs (lncRNAs), microRNAs (miRNAs), circular RNAs (circRNAs), PIWI-interacting RNAs (piRNAs), and others, can serve as scaffolds, regulators, or clients within the LLPS droplets, thereby influencing both normal cellular organization and disease processes. This review provides an overview of current research on how ncRNAs contribute to LLPS across different cellular localizations and contexts, covering physiological condensates, disease linked phase separation, underlying molecular mechanisms, and emerging therapeutic implications.
{"title":"Noncoding RNAs are indispensable architects and regulators of biomolecular condensates","authors":"Shiyuan Chen , Canchen Wang , Junyi Hu, Ting Luo, Qian Li, Hui Shen","doi":"10.1016/j.ncrna.2026.01.003","DOIUrl":"10.1016/j.ncrna.2026.01.003","url":null,"abstract":"<div><div>Liquid-liquid phase separation (LLPS) is a biophysical mechanism by which certain biomolecules demix from the cytosol or nucleoplasm to form membraneless organelles. These droplet-like assemblies are dynamic and reversible, allowing selective enrichment of specific proteins and nucleic acids while excluding others. Classical examples include the nucleolus, P-bodies, and stress granules, all of which exhibit liquid-like behaviors such as rapid fusion, fission, and molecular exchange. Most importantly, the LLPS property has been implicated with a plethora of physiological and pathological processes. Historically, research on LLPS focused on protein drivers, especially RNA-binding proteins (RBPs) with low complexity domains or intrinsically disordered regions, contributing to multivalent weak interactions. However, it is now clear that RNA molecules especially noncoding RNAs are integral components and often active modulators of these condensates. Noncoding RNAs, including long noncoding RNAs (lncRNAs), microRNAs (miRNAs), circular RNAs (circRNAs), PIWI-interacting RNAs (piRNAs), and others, can serve as scaffolds, regulators, or clients within the LLPS droplets, thereby influencing both normal cellular organization and disease processes. This review provides an overview of current research on how ncRNAs contribute to LLPS across different cellular localizations and contexts, covering physiological condensates, disease linked phase separation, underlying molecular mechanisms, and emerging therapeutic implications.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"18 ","pages":"Pages 12-21"},"PeriodicalIF":4.7,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981888","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}
Pub Date : 2026-01-15DOI: 10.1016/j.ncrna.2026.01.004
Bohao Zhao , Jiawei Cai , Miaocheng Wang , Jiali Li , Shuyu Yao , Zhiyuan Bao , Yang Chen , Xinsheng Wu
Exosomes are nanoscale particles that participate in multiple biological processes and are secreted by various cell types. Exosomes derived from dermal papilla cells (DPC-Exos) regulate hair follicle (HF) growth and development. In this study, HF development-related genes were significantly expressed in low-passage dermal papilla cells (DPCs). Low-passage DPC-Exos promoted hair follicle stem cell (HFSC) proliferation. After the collection of DPC-Exos, miRNA sequencing identified 36 differentially expressed (DE) miRNAs between low-passage and high-passage DPC-Exos. Among these, miR-218–5p was significantly upregulated in low-passage DPC-Exos and dysregulated HF growth and development-related gene expression in HFSCs. Furthermore, the transport mechanism of exosomal miR-218–5p from DPCs is into HFSCs was verified. RNA sequencing of HFSCs treated with exosomal miR-218–5p identified differentially expressed genes (DEGs). The results indicated involvement of miR-218–5p in signaling pathways related to HF growth and development. Additionally, in vitro HF organ culture experiments demonstrated that exosomal miR-218–5p actively promotes hair growth. In summary, low-passage DPC-Exos enhance HFSC proliferation. Exosomal miR-218–5p may serve as a biomarker and therapeutic target for human hair disorders and as a tool to improve wool production in mammals.
{"title":"Exosomal miRNA-218–5p derived from low-passage dermal papilla cells modulates hair follicle growth and development","authors":"Bohao Zhao , Jiawei Cai , Miaocheng Wang , Jiali Li , Shuyu Yao , Zhiyuan Bao , Yang Chen , Xinsheng Wu","doi":"10.1016/j.ncrna.2026.01.004","DOIUrl":"10.1016/j.ncrna.2026.01.004","url":null,"abstract":"<div><div>Exosomes are nanoscale particles that participate in multiple biological processes and are secreted by various cell types. Exosomes derived from dermal papilla cells (DPC-Exos) regulate hair follicle (HF) growth and development. In this study, HF development-related genes were significantly expressed in low-passage dermal papilla cells (DPCs). Low-passage DPC-Exos promoted hair follicle stem cell (HFSC) proliferation. After the collection of DPC-Exos, miRNA sequencing identified 36 differentially expressed (DE) miRNAs between low-passage and high-passage DPC-Exos. Among these, miR-218–5p was significantly upregulated in low-passage DPC-Exos and dysregulated HF growth and development-related gene expression in HFSCs. Furthermore, the transport mechanism of exosomal miR-218–5p from DPCs is into HFSCs was verified. RNA sequencing of HFSCs treated with exosomal miR-218–5p identified differentially expressed genes (DEGs). The results indicated involvement of miR-218–5p in signaling pathways related to HF growth and development. Additionally, <em>in vitro</em> HF organ culture experiments demonstrated that exosomal miR-218–5p actively promotes hair growth. In summary, low-passage DPC-Exos enhance HFSC proliferation. Exosomal miR-218–5p may serve as a biomarker and therapeutic target for human hair disorders and as a tool to improve wool production in mammals.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"18 ","pages":"Pages 1-11"},"PeriodicalIF":4.7,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145963108","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}
Pub Date : 2026-01-06DOI: 10.1016/j.ncrna.2025.12.004
Jiayi Chen , Juanmei Gao
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.
{"title":"Mechanistic roles of long non-coding RNAs in gastric cancer therapy resistance","authors":"Jiayi Chen , 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":"2026-01-06","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}