Pub Date : 2026-06-01Epub 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":"2026-06-01","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}
Nuclear microRNAs represent a novel class of non-canonical miRNAs localized within the nucleus, distinguished from classical cytoplasmic miRNAs by their unique ability to activate gene transcription. Classical miRNAs, approximately 22 nucleotides in length, regulate target mRNA stability or translational efficiency, primarily leading to translation inhibition or mRNA degradation. In contrast, nuclear microRNAs, measuring 18–22 nucleotides, do not rely on Dicer processing and are directly cleaved from precursor miRNAs by Drosha. Their nuclear localization and regulation of gene transcription contrast sharply with the suppressive role of classical miRNAs. Nuclear microRNAs are transcribed and modified within the nucleus via RNA polymerase II, undergoing processing similar to conventional miRNAs but diverging in their final nuclear localization and functional mechanisms. They interact with key regulatory elements such as promoters, enhancers, or gene bodies, modulating gene expression at the transcriptional level. This interaction can occur through RNA-RNA scaffolding, RNA-DNA hybrid formation, or RNA-DNA triplex formation, influencing chromatin structure and transcription factor accessibility. Nuclear microRNAs demonstrate diverse regulatory functions, acting as enhancer triggers, promoter regulators, and transcriptional amplifiers. They recruit transcription factors or alter chromatin's epigenetic state to promote transcription, impacting cellular processes such as hematopoiesis, differentiation, and apoptosis. In particular, nuclear microRNAs have been implicated in cancer progression and therapeutic responses, with the potential to orchestrate oncogene networks and tumor-suppressive pathways. Despite their promising therapeutic potential, clinical translation of nuclear microRNAs faces challenges such as delivery precision, immunogenicity, regulatory complexity, and ethical governance. Advancing nuclear delivery systems and mechanistic studies are essential to overcome these limitations and harness the full potential of nuclear microRNAs in gene regulation therapeutics. As research progresses, nuclear microRNAs may revolutionize RNA therapeutics by enabling transcriptional-level disease intervention.
{"title":"The paradox of nuclear miRNAs: Mechanisms, therapeutic potential, and future directions","authors":"Kexin Yang , Chunmei Zhang , Zelong Zhao, Minmin Feng, Linxia Song, Zhenbiao Xu","doi":"10.1016/j.ncrna.2026.01.010","DOIUrl":"10.1016/j.ncrna.2026.01.010","url":null,"abstract":"<div><div>Nuclear microRNAs represent a novel class of non-canonical miRNAs localized within the nucleus, distinguished from classical cytoplasmic miRNAs by their unique ability to activate gene transcription. Classical miRNAs, approximately 22 nucleotides in length, regulate target mRNA stability or translational efficiency, primarily leading to translation inhibition or mRNA degradation. In contrast, nuclear microRNAs, measuring 18–22 nucleotides, do not rely on Dicer processing and are directly cleaved from precursor miRNAs by Drosha. Their nuclear localization and regulation of gene transcription contrast sharply with the suppressive role of classical miRNAs. Nuclear microRNAs are transcribed and modified within the nucleus via RNA polymerase II, undergoing processing similar to conventional miRNAs but diverging in their final nuclear localization and functional mechanisms. They interact with key regulatory elements such as promoters, enhancers, or gene bodies, modulating gene expression at the transcriptional level. This interaction can occur through RNA-RNA scaffolding, RNA-DNA hybrid formation, or RNA-DNA triplex formation, influencing chromatin structure and transcription factor accessibility. Nuclear microRNAs demonstrate diverse regulatory functions, acting as enhancer triggers, promoter regulators, and transcriptional amplifiers. They recruit transcription factors or alter chromatin's epigenetic state to promote transcription, impacting cellular processes such as hematopoiesis, differentiation, and apoptosis. In particular, nuclear microRNAs have been implicated in cancer progression and therapeutic responses, with the potential to orchestrate oncogene networks and tumor-suppressive pathways. Despite their promising therapeutic potential, clinical translation of nuclear microRNAs faces challenges such as delivery precision, immunogenicity, regulatory complexity, and ethical governance. Advancing nuclear delivery systems and mechanistic studies are essential to overcome these limitations and harness the full potential of nuclear microRNAs in gene regulation therapeutics. As research progresses, nuclear microRNAs may revolutionize RNA therapeutics by enabling transcriptional-level disease intervention.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"18 ","pages":"Pages 108-117"},"PeriodicalIF":4.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189611","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":"2026-06-01","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 : 2026-06-01Epub 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":"2026-06-01","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}
Pub Date : 2026-06-01Epub Date: 2026-02-03DOI: 10.1016/j.ncrna.2026.01.012
Chao Xu , Beibei Zhou , Fan Bai , Hang Sun , Cuiping Zhang , Zhenlun Wu , Jiachuan Hou , Jinjing Xie , Yanbin Wei , Libin Pan , Ruiqi Yang , Hongjie Dong , Guihua Zhao , Jingyu Yang , Jianwei Zhou , Ruili Wu , Kun Yin
Aberrant expression of miR-155 has been implicated in the pathogenesis of inflammatory bowel disease (IBD), where its dysregulation may contribute to impaired intestinal barrier integrity and sustained inflammation. However, the precise role of miR-155 in the development of ulcerative colitis (UC) remains incompletely understood. This case-control study aimed to evaluate the association between polymorphisms of MIR155HG gene and susceptibility to UC in a Chinese Han population. The study included 84 UC patients and 216 matched healthy controls. Four single nucleotide polymorphisms (SNPs) of MIR155HG (rs1893650, rs2282471, rs2829803, and rs2829806) were genotyped using the Sequenom MassARRAY platform. Function prediction of SNPs were conducted using RNAfold databases. We observed MIR155HG rs2282471 polymorphism was significantly associated with a reduced risk of UC. Specifically, the minor T allele, homozygous TT genotype, and the recessive genetic model (TT vs CT + CC) of rs2282471 conferred protective effect to the disease. The stratified analysis indicated this protective effect was more pronounced in male patients. Furthermore, haplotype analysis showed a strong linkage disequilibrium among the four SNPs and identified a specific haplotype (TGTT) that was also associated with decreased UC risk. No significant correlations were observed between four SNPs and clinical features such as disease severity or lesion location. Structure prediction suggested that rs2282471 may influence the secondary structure of miR-155. These findings provided the first evidence that the MIR155HG rs2282471 polymorphism were associated with decreased UC susceptibility in the Chinese Han population, suggesting MIR155HG might be a predictive biomarker for risk of UC.
miR-155的异常表达与炎症性肠病（IBD）的发病机制有关，其失调可能导致肠屏障完整性受损和持续炎症。然而，miR-155在溃疡性结肠炎（UC）发展中的确切作用仍不完全清楚。本病例对照研究旨在评估中国汉族人群中MIR155HG基因多态性与UC易感性之间的关系。该研究包括84名UC患者和216名匹配的健康对照。利用Sequenom MassARRAY平台对MIR155HG的4个单核苷酸多态性（rs1893650、rs2282471、rs2829803和rs2829806）进行基因分型。使用RNAfold数据库进行snp的功能预测。我们观察到MIR155HG rs2282471多态性与UC风险降低显著相关。具体来说，rs2282471的次要T等位基因、纯合子TT基因型和隐性遗传模型（TT vs CT + CC）对疾病具有保护作用。分层分析表明，这种保护作用在男性患者中更为明显。此外，单倍型分析显示，四个snp之间存在强烈的连锁不平衡，并确定了一个特定的单倍型（TGTT），该单倍型也与UC风险降低有关。4个snp与疾病严重程度或病变部位等临床特征之间无显著相关性。结构预测提示rs2282471可能影响miR-155的二级结构。这些发现提供了MIR155HG rs2282471多态性与中国汉族人群UC易感性降低相关的第一个证据，表明MIR155HG可能是UC风险的预测性生物标志物。
{"title":"Analysis of MIR155HG gene polymorphisms and ulcerative colitis susceptibility in the Chinese Han Population","authors":"Chao Xu , Beibei Zhou , Fan Bai , Hang Sun , Cuiping Zhang , Zhenlun Wu , Jiachuan Hou , Jinjing Xie , Yanbin Wei , Libin Pan , Ruiqi Yang , Hongjie Dong , Guihua Zhao , Jingyu Yang , Jianwei Zhou , Ruili Wu , Kun Yin","doi":"10.1016/j.ncrna.2026.01.012","DOIUrl":"10.1016/j.ncrna.2026.01.012","url":null,"abstract":"<div><div>Aberrant expression of miR-155 has been implicated in the pathogenesis of inflammatory bowel disease (IBD), where its dysregulation may contribute to impaired intestinal barrier integrity and sustained inflammation. However, the precise role of miR-155 in the development of ulcerative colitis (UC) remains incompletely understood. This case-control study aimed to evaluate the association between polymorphisms of <em>MIR155HG</em> gene and susceptibility to UC in a Chinese Han population. The study included 84 UC patients and 216 matched healthy controls. Four single nucleotide polymorphisms (SNPs) of <em>MIR155HG</em> (rs1893650, rs2282471, rs2829803, and rs2829806) were genotyped using the Sequenom MassARRAY platform. Function prediction of SNPs were conducted using RNAfold databases. We observed <em>MIR155HG</em> rs2282471 polymorphism was significantly associated with a reduced risk of UC. Specifically, the minor T allele, homozygous TT genotype, and the recessive genetic model (TT vs CT + CC) of rs2282471 conferred protective effect to the disease. The stratified analysis indicated this protective effect was more pronounced in male patients. Furthermore, haplotype analysis showed a strong linkage disequilibrium among the four SNPs and identified a specific haplotype (TGTT) that was also associated with decreased UC risk. No significant correlations were observed between four SNPs and clinical features such as disease severity or lesion location. Structure prediction suggested that rs2282471 may influence the secondary structure of miR-155. These findings provided the first evidence that the <em>MIR155HG</em> rs2282471 polymorphism were associated with decreased UC susceptibility in the Chinese Han population, suggesting <em>MIR155HG</em> might be a predictive biomarker for risk of UC.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"18 ","pages":"Pages 92-100"},"PeriodicalIF":4.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146190037","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 : 2026-06-01Epub Date: 2026-02-03DOI: 10.1016/j.ncrna.2026.01.011
Ganesh Koshre , Misbah Khan , Swetha Rajasekaran , Amity L. Manning , James A. Walker , Wayne O. Miles
DICER1 is a key processing enzyme required for the generation of mature and active miRNAs. Mutations that diminish DICER1 function result in widespread changes in miRNA levels, resulting in changes in the transcriptome and cellular phenotypes. Previously, we have found that mutations within the 3′UTR of the Dicer1 mRNA diminish DICER1 protein levels and miRNA production. Triple negative breast cancer cells that contain these mutations have slower growth and migration and diminished tumorigenic potential. By comparing the transcriptome and miRNA profile of these cells, we find that miR30d-5p are significantly reduced in DICER1 mutant cells. This reduction in miR30d-5p results in increased mRNA stability and protein levels of the miR30d-5p target, SNAIL, a transcription factor that promotes the transcription of genes required for mesenchymal cell fates. We show that elevated SNAIL protein levels induce the upregulation of SNAIL target genes that can be partially rescued by the addition of miR30d-5p. Our results highlight the key role for DICER1 and miRNA levels in modulating cell fate in breast cancer.
{"title":"DICER1 dysregulation triggers reprogramming of a specific miRNA subset, promotes mesenchymal cell fates and slows TNBC tumorigenic phenotypes","authors":"Ganesh Koshre , Misbah Khan , Swetha Rajasekaran , Amity L. Manning , James A. Walker , Wayne O. Miles","doi":"10.1016/j.ncrna.2026.01.011","DOIUrl":"10.1016/j.ncrna.2026.01.011","url":null,"abstract":"<div><div>DICER1 is a key processing enzyme required for the generation of mature and active miRNAs. Mutations that diminish DICER1 function result in widespread changes in miRNA levels, resulting in changes in the transcriptome and cellular phenotypes. Previously, we have found that mutations within the 3′UTR of the <em>Dicer1</em> mRNA diminish DICER1 protein levels and miRNA production. Triple negative breast cancer cells that contain these mutations have slower growth and migration and diminished tumorigenic potential. By comparing the transcriptome and miRNA profile of these cells, we find that miR30d-5p are significantly reduced in DICER1 mutant cells. This reduction in miR30d-5p results in increased mRNA stability and protein levels of the miR30d-5p target, SNAIL, a transcription factor that promotes the transcription of genes required for mesenchymal cell fates. We show that elevated SNAIL protein levels induce the upregulation of SNAIL target genes that can be partially rescued by the addition of miR30d-5p. Our results highlight the key role for DICER1 and miRNA levels in modulating cell fate in breast cancer.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"18 ","pages":"Pages 101-107"},"PeriodicalIF":4.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146166977","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 : 2026-06-01Epub Date: 2025-08-26DOI: 10.1016/j.ncrna.2025.08.004
Cheng Cheng , Yi Yang , Youshan Qu
Image-guided radiotherapy (IGRT) is a crucial technique in cervical cancer treatment, enabling precise targeting of tumor tissues while minimizing radiation exposure to surrounding healthy tissues. Kilovoltage cone-beam computed tomography (KVCBCT) is commonly used for IGRT, allowing for real-time imaging of tumor position and anatomy during treatment sessions. However, the selection of optimal landmarks for image registration in IGRT remains a topic of investigation. This study investigated role of IGRT in cervical cancer treatment by analyzing eight cervical cancer patients treated at University Hospital between April 2019 and April 2021. All patients underwent KVCBCT IGRT treatment, and initial treatment images were analyzed. Landmarks including bone, coccyx, and tumor regions were selected for image registration with reference images using both automatic and manual registration methods. Correlation was also sought with several non-coding RNAs, particularly miR-21 and miR-34a. The registration results of different landmarks were observed and compared to evaluate their accuracy and reliability. The study revealed that there were no statistically significant differences in positional errors between bone and tumor landmarks in three directions. However, statistically significant differences in positional errors were observed in the XY and Z directions compared to the coccyx landmark. The miRNA levels correlated with documented trends in cervical cancer. These findings suggest that selecting bone and tumor landmarks as optimal registration points for image registration can enhance the effectiveness of IGRT in treating cervical cancer. By employing both automatic and manual registration methods and analyzing the differences in registration results among various landmarks, this study provides insights into the role of IGRT in cervical cancer treatment. The results indicate that choosing bone and tumor landmarks as optimal registration points can improve the accuracy and efficacy of IGRT, leading to better treatment outcomes and reduced side effects. These findings offer scientific evidence and practical guidance for the utilization of IGRT in cervical cancer treatment, providing valuable technical support for future clinical practice.
{"title":"Investigation of the impact of image-guided radiotherapy selection on image registration results and non-coding RNAs for cervical cancer patients","authors":"Cheng Cheng , Yi Yang , Youshan Qu","doi":"10.1016/j.ncrna.2025.08.004","DOIUrl":"10.1016/j.ncrna.2025.08.004","url":null,"abstract":"<div><div>Image-guided radiotherapy (IGRT) is a crucial technique in cervical cancer treatment, enabling precise targeting of tumor tissues while minimizing radiation exposure to surrounding healthy tissues. Kilovoltage cone-beam computed tomography (KVCBCT) is commonly used for IGRT, allowing for real-time imaging of tumor position and anatomy during treatment sessions. However, the selection of optimal landmarks for image registration in IGRT remains a topic of investigation. This study investigated role of IGRT in cervical cancer treatment by analyzing eight cervical cancer patients treated at University Hospital between April 2019 and April 2021. All patients underwent KVCBCT IGRT treatment, and initial treatment images were analyzed. Landmarks including bone, coccyx, and tumor regions were selected for image registration with reference images using both automatic and manual registration methods. Correlation was also sought with several non-coding RNAs, particularly miR-21 and miR-34a. The registration results of different landmarks were observed and compared to evaluate their accuracy and reliability. The study revealed that there were no statistically significant differences in positional errors between bone and tumor landmarks in three directions. However, statistically significant differences in positional errors were observed in the XY and Z directions compared to the coccyx landmark. The miRNA levels correlated with documented trends in cervical cancer. These findings suggest that selecting bone and tumor landmarks as optimal registration points for image registration can enhance the effectiveness of IGRT in treating cervical cancer. By employing both automatic and manual registration methods and analyzing the differences in registration results among various landmarks, this study provides insights into the role of IGRT in cervical cancer treatment. The results indicate that choosing bone and tumor landmarks as optimal registration points can improve the accuracy and efficacy of IGRT, leading to better treatment outcomes and reduced side effects. These findings offer scientific evidence and practical guidance for the utilization of IGRT in cervical cancer treatment, providing valuable technical support for future clinical practice.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"18 ","pages":"Pages 87-91"},"PeriodicalIF":4.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146167018","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 : 2026-06-01Epub 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":"2026-06-01","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 : 2026-06-01Epub 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":"2026-06-01","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 : 2026-06-01Epub 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":"2026-06-01","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}
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