Pub Date : 2025-07-06DOI: 10.1016/j.ncrna.2025.07.002
Xia Cai , Hui Shan , Jiaojiao Wang , Jiaxin Qin , Huiling Gong , Jun Cai , Jin He
Small RNAs (sRNAs) are widely used by bacteria to regulate diverse biological processes. Although they are generally considered “non-coding”, some sRNAs (called dual-function sRNAs) have been found to encode small proteins, which are usually less than 50 amino acids in length and have long been overlooked due to significant challenges in their annotation and biochemical detection. However, in the past few decades, an increasing number of small proteins encoded by dual-function sRNAs have been reported. Previous reviews of dual-function sRNAs have mainly focused on their base-pairing nucleic acid functions, with less emphasis on the nature of their translated peptides, resulting in limited understanding of their full functional scope. This article reviews ten small proteins encoded by dual-function sRNAs and introduces their physiological functions, interacting protein partners, and the research methods used, aiming to provide new perspectives and directions for the study of small proteins and enhance understanding of bacterial regulatory mechanisms mediated by dual-function sRNAs.
{"title":"Overview of small proteins encoded by bacterial dual-function small RNAs","authors":"Xia Cai , Hui Shan , Jiaojiao Wang , Jiaxin Qin , Huiling Gong , Jun Cai , Jin He","doi":"10.1016/j.ncrna.2025.07.002","DOIUrl":"10.1016/j.ncrna.2025.07.002","url":null,"abstract":"<div><div>Small RNAs (sRNAs) are widely used by bacteria to regulate diverse biological processes. Although they are generally considered “non-coding”, some sRNAs (called dual-function sRNAs) have been found to encode small proteins, which are usually less than 50 amino acids in length and have long been overlooked due to significant challenges in their annotation and biochemical detection. However, in the past few decades, an increasing number of small proteins encoded by dual-function sRNAs have been reported. Previous reviews of dual-function sRNAs have mainly focused on their base-pairing nucleic acid functions, with less emphasis on the nature of their translated peptides, resulting in limited understanding of their full functional scope. This article reviews ten small proteins encoded by dual-function sRNAs and introduces their physiological functions, interacting protein partners, and the research methods used, aiming to provide new perspectives and directions for the study of small proteins and enhance understanding of bacterial regulatory mechanisms mediated by dual-function sRNAs.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"15 ","pages":"Pages 44-50"},"PeriodicalIF":5.9,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-03DOI: 10.1016/j.ncrna.2025.07.001
Yina Li , Nan Wang , Jinying Hu, Minlan Luo, Na Zhang, Lili Gao
Aims
This study investigates how plasma exosomal miRNAs regulate core fucosylation (CF)-modified targets to influence autophagy and fibrosis in idiopathic pulmonary fibrosis (IPF), aiming to identify novel therapeutic strategies targeting dysregulated alveolar epithelial cell (AEC) autophagy.
Materials and methods
Plasma exosomes from IPF patients and healthy controls were isolated via ultracentrifugation, validated by TEM, nanoparticle tracking analysis (NTA), and Western blot (CD9/CD81). Exosomal miRNA profiling employed high-throughput sequencing, with TargetScan/miRanda predicting target genes. A549 and MLE-12 cells assessed exosome uptake (PKH67 labeling) and miRNA-mRNA interactions (dual-luciferase assays). CF modification was analyzed via immunoprecipitation/Western blot. In vivo validation used bleomycin (BLM)-induced fibrosis models in alveolar epithelial-specific FUT8-knockout (CKO) mice.
Key findings
IPF plasma exosomes suppressed autophagy and exacerbated fibrosis in AECs. miR-15a-5p was markedly downregulated in IPF exosomes. Overexpression of miR-15a-5p reversed BLM-induced autophagy inhibition and fibrosis. Mechanistically, miR-15a-5p directly targeted IGF1R, a CF-modified protein. Reduced miR-15a-5p elevated IGF1R expression, activating PI3K/AKT to inhibit autophagy and promote fibrosis.
Significance
This study identifies miR-15a-5p as a critical regulator of CF-modified IGF1R in IPF pathogenesis. Its downregulation drives PI3K/AKT-mediated autophagy suppression, accelerating fibrosis. Restoring miR-15a-5p or targeting IGF1R/PI3K/AKT signaling may offer novel therapeutic avenues for IPF.
本研究探讨血浆外泌体mirna如何调节核心聚焦化（CF）修饰的靶点影响特发性肺纤维化（IPF）的自噬和纤维化，旨在确定针对失调肺泡上皮细胞（AEC）自噬的新治疗策略。材料和方法采用超离心分离IPF患者和健康对照的血浆外泌体，通过TEM、纳米颗粒跟踪分析（NTA）和Western blot （CD9/CD81）进行验证。外泌体miRNA分析采用高通量测序，TargetScan/miRanda预测靶基因。A549和MLE-12细胞评估外泌体摄取（PKH67标记）和miRNA-mRNA相互作用（双荧光素酶测定）。通过免疫沉淀/Western blot分析CF修饰。在肺泡上皮特异性fut8敲除（CKO）小鼠中使用博来霉素（BLM）诱导的纤维化模型进行体内验证。关键发现sipf血浆外泌体抑制aec的自噬并加重纤维化。miR-15a-5p在IPF外泌体中明显下调。过表达miR-15a-5p可逆转blm诱导的自噬抑制和纤维化。在机制上，miR-15a-5p直接靶向IGF1R，一种cf修饰的蛋白。miR-15a-5p降低，IGF1R表达升高，激活PI3K/AKT抑制自噬，促进纤维化。本研究发现miR-15a-5p在IPF发病机制中是cf修饰的IGF1R的关键调节因子。其下调驱动PI3K/ akt介导的自噬抑制，加速纤维化。恢复miR-15a-5p或靶向IGF1R/PI3K/AKT信号通路可能为IPF提供新的治疗途径。
{"title":"The mechanism of plasma exosome miR-15a-5p targeting the CF-modified protein IGF1R to regulate alveolar epithelial autophagy and influence pulmonary interstitial fibrosis","authors":"Yina Li , Nan Wang , Jinying Hu, Minlan Luo, Na Zhang, Lili Gao","doi":"10.1016/j.ncrna.2025.07.001","DOIUrl":"10.1016/j.ncrna.2025.07.001","url":null,"abstract":"<div><h3>Aims</h3><div>This study investigates how plasma exosomal miRNAs regulate core fucosylation (CF)-modified targets to influence autophagy and fibrosis in idiopathic pulmonary fibrosis (IPF), aiming to identify novel therapeutic strategies targeting dysregulated alveolar epithelial cell (AEC) autophagy.</div></div><div><h3>Materials and methods</h3><div>Plasma exosomes from IPF patients and healthy controls were isolated via ultracentrifugation, validated by TEM, nanoparticle tracking analysis (NTA), and Western blot (CD9/CD81). Exosomal miRNA profiling employed high-throughput sequencing, with TargetScan/miRanda predicting target genes. A549 and MLE-12 cells assessed exosome uptake (PKH67 labeling) and miRNA-mRNA interactions (dual-luciferase assays). CF modification was analyzed via immunoprecipitation/Western blot. In vivo validation used bleomycin (BLM)-induced fibrosis models in alveolar epithelial-specific FUT8-knockout (CKO) mice.</div></div><div><h3>Key findings</h3><div>IPF plasma exosomes suppressed autophagy and exacerbated fibrosis in AECs. miR-15a-5p was markedly downregulated in IPF exosomes. Overexpression of miR-15a-5p reversed BLM-induced autophagy inhibition and fibrosis. Mechanistically, miR-15a-5p directly targeted IGF1R, a CF-modified protein. Reduced miR-15a-5p elevated IGF1R expression, activating PI3K/AKT to inhibit autophagy and promote fibrosis.</div></div><div><h3>Significance</h3><div>This study identifies miR-15a-5p as a critical regulator of CF-modified IGF1R in IPF pathogenesis. Its downregulation drives PI3K/AKT-mediated autophagy suppression, accelerating fibrosis. Restoring miR-15a-5p or targeting IGF1R/PI3K/AKT signaling may offer novel therapeutic avenues for IPF.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"15 ","pages":"Pages 51-64"},"PeriodicalIF":5.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695462","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 : 2025-06-23DOI: 10.1016/j.ncrna.2025.06.004
Dong-Li Zhu , Yan Zhang , Xiao-Yu Zhang , Zi-Han Qiu , Ke Li , Xiao-Rong Zhou , Zhen-Zhen He , Xiao-Feng Chen , Shan-Shan Dong , Wen Tian , Ya-Kang Wang , Tie-Lin Yang , Bo Yang , Yan Guo
Background
Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass and microarchitectural deterioration of bone tissue. Our previous investigation provided preliminary evidence that single nucleotide polymorphisms (SNPs) may functionally interact with the LINC00339, potentially contributing to the pathogenesis and progression of osteoporosis through undefined molecular pathways. However, the exact mechanistic basis of LINC00339's involvement in osteoporotic bone remodeling remains incompletely characterized and warrants systematic exploration.
Methods
We analyzed the differentially expressed of LINC003339 in different bone tissues by qRT-PCR. ALP and Alizarin red S (ARS) staining were conducted in stably knocked-down and overexpressed of LINC00339 cell lines. RNA fluorescence in situ hybridization (FISH) assays were used to detect the subcellular location of LINC00339. The mechanism of LINC00339 regulating cell division cycle 42 (CDC42) was explored by RNA-protein pull-down, RNA immunoprecipitation (RIP) and Co-IP assays.
Results
This study demonstrated significant upregulation of LINC00339 in bone tissue specimens derived from osteoporosis patients compared to healthy controls. Functional analyses revealed that LINC00339 dysregulation exhibited an inverse correlation with osteogenic differentiation capacity across multiple osteoblast cell models. Subcellular localization analysis via FISH confirmed the predominant cytoplasmic distribution of LINC00339 in bone cells. Mechanistically, RNA-protein pull-down assays combined with RNA immunoprecipitation (RIP) identified poly (ADP-Ribose) polymerase 1 (PARP1) as a direct binding partner of LINC00339. Further investigation established that the LINC00339-PARP1 axis cooperatively modulates transcriptional programs critical to bone homeostasis, potentially driving pathogenic mechanisms underlying osteoporosis progression. Notably, integrated transcriptomic and rescue experiments revealed that LINC00339 and PARP1 coregulate CDC42 expression through post-transcriptional regulatory mechanisms.
Conclusions
The identification of the LINC00339-PARP1-CDC42 regulatory axis elucidates a novel molecular mechanism contributing to osteoporosis pathogenesis. This discovery not only advances our understanding of epigenetic regulation in bone remodeling but also positions the LINC00339-PARP1 interaction as a potential therapeutic target for modulating osteoblast dysfunction. Importantly, these findings establish a conceptual framework for lncRNA-driven interventions in skeletal disorders, highlighting the translational potential of targeting RNA-protein complexes to restore bone homeostasis.
{"title":"Long noncoding RNA LINC00339 promotes osteoporosis development via modulating of regulator CDC42 by binding PARP1","authors":"Dong-Li Zhu , Yan Zhang , Xiao-Yu Zhang , Zi-Han Qiu , Ke Li , Xiao-Rong Zhou , Zhen-Zhen He , Xiao-Feng Chen , Shan-Shan Dong , Wen Tian , Ya-Kang Wang , Tie-Lin Yang , Bo Yang , Yan Guo","doi":"10.1016/j.ncrna.2025.06.004","DOIUrl":"10.1016/j.ncrna.2025.06.004","url":null,"abstract":"<div><h3>Background</h3><div>Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass and microarchitectural deterioration of bone tissue. Our previous investigation provided preliminary evidence that single nucleotide polymorphisms (SNPs) may functionally interact with the LINC00339, potentially contributing to the pathogenesis and progression of osteoporosis through undefined molecular pathways. However, the exact mechanistic basis of LINC00339's involvement in osteoporotic bone remodeling remains incompletely characterized and warrants systematic exploration.</div></div><div><h3>Methods</h3><div>We analyzed the differentially expressed of LINC003339 in different bone tissues by qRT-PCR. ALP and Alizarin red S (ARS) staining were conducted in stably knocked-down and overexpressed of LINC00339 cell lines. RNA fluorescence in situ hybridization (FISH) assays were used to detect the subcellular location of LINC00339. The mechanism of LINC00339 regulating cell division cycle 42 (CDC42) was explored by RNA-protein pull-down, RNA immunoprecipitation (RIP) and Co-IP assays.</div></div><div><h3>Results</h3><div>This study demonstrated significant upregulation of LINC00339 in bone tissue specimens derived from osteoporosis patients compared to healthy controls. Functional analyses revealed that LINC00339 dysregulation exhibited an inverse correlation with osteogenic differentiation capacity across multiple osteoblast cell models. Subcellular localization analysis via FISH confirmed the predominant cytoplasmic distribution of LINC00339 in bone cells. Mechanistically, RNA-protein pull-down assays combined with RNA immunoprecipitation (RIP) identified poly (ADP-Ribose) polymerase 1 (PARP1) as a direct binding partner of LINC00339. Further investigation established that the LINC00339-PARP1 axis cooperatively modulates transcriptional programs critical to bone homeostasis, potentially driving pathogenic mechanisms underlying osteoporosis progression. Notably, integrated transcriptomic and rescue experiments revealed that LINC00339 and PARP1 coregulate CDC42 expression through post-transcriptional regulatory mechanisms.</div></div><div><h3>Conclusions</h3><div>The identification of the LINC00339-PARP1-CDC42 regulatory axis elucidates a novel molecular mechanism contributing to osteoporosis pathogenesis. This discovery not only advances our understanding of epigenetic regulation in bone remodeling but also positions the LINC00339-PARP1 interaction as a potential therapeutic target for modulating osteoblast dysfunction. Importantly, these findings establish a conceptual framework for lncRNA-driven interventions in skeletal disorders, highlighting the translational potential of targeting RNA-protein complexes to restore bone homeostasis.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"15 ","pages":"Pages 18-28"},"PeriodicalIF":5.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654332","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 : 2025-06-23DOI: 10.1016/j.ncrna.2025.06.003
Paula Aparicio , Tresa López-Royo , David Navarrete-Villanueva , Alba María Gómez Cabello , Marcela González-Gross , Ignacio Ara , Germán Vicente-Rodríguez , Rosario Osta , Raquel Manzano
Sarcopenia, the loss of muscle mass and function generally associated to age, leads to increased dependence and mortality in older adults. Despite its clinical significance, unclear molecular mechanisms hinder the development of universal diagnostic and therapeutic monitoring methods. Recent research suggests long non-coding RNAs (lncRNAs) as potential biomarkers for muscle damage and sarcopenia. This study investigates the role of six specific lncRNAs as biomarkers for diagnosing and monitoring sarcopenia following physical training. For this purpose, an initial cohort of participants was divided into two experiments: Trial 1, a cross-sectional study comprising 54 sarcopenic patients and 29 robust controls, both including men and women; Trial 2, a non-randomized controlled trial, where the same sarcopenic patients from Trial 1 were divided in two groups: a Control Group (CG, n = 15); and a Trained Group (TG, n = 22). RNA was extracted from serum samples for all the participants, and the expression of 6 lncRNA (PVT1, HOTAIR, MALAT1, NEAT1, GAS5, H19), selected from the literature, was quantified by RT-PCR and compared between the different groups. Statistical evaluation uncovered four lncRNAs with significantly distinct expression in Trial 1: PVT1 (LOG2FC = 1.194), GAS5 (LOG2FC = 0.8224), NEAT1 (LOG2FC = 1.497) and H19 (LOG2FC = −0.9958) and three lncRNA significantly different between TG and CG in Trial 2 (PVT1 (LOG2FC = −1.796), MALAT1 (LOG2FC = 2.834) and H19 (LOG2FC = 1.355). Among them, NEAT 1 stands aout as promissing diagnostic marker ans PVT1 and H19 may serve as both diagnosis and treatment monitoring, altough further validation in larger cohorts is needed to confirm these results.
{"title":"Serum lncRNAs NEAT1, PVT1 and H19 as novel biomarkers for sarcopenia diagnosis and treatment response","authors":"Paula Aparicio , Tresa López-Royo , David Navarrete-Villanueva , Alba María Gómez Cabello , Marcela González-Gross , Ignacio Ara , Germán Vicente-Rodríguez , Rosario Osta , Raquel Manzano","doi":"10.1016/j.ncrna.2025.06.003","DOIUrl":"10.1016/j.ncrna.2025.06.003","url":null,"abstract":"<div><div>Sarcopenia, the loss of muscle mass and function generally associated to age, leads to increased dependence and mortality in older adults. Despite its clinical significance, unclear molecular mechanisms hinder the development of universal diagnostic and therapeutic monitoring methods. Recent research suggests long non-coding RNAs (lncRNAs) as potential biomarkers for muscle damage and sarcopenia. This study investigates the role of six specific lncRNAs as biomarkers for diagnosing and monitoring sarcopenia following physical training. For this purpose, an initial cohort of participants was divided into two experiments: Trial 1, a cross-sectional study comprising 54 sarcopenic patients and 29 robust controls, both including men and women; Trial 2, a non-randomized controlled trial, where the same sarcopenic patients from Trial 1 were divided in two groups: a Control Group (CG, n = 15); and a Trained Group (TG, n = 22). RNA was extracted from serum samples for all the participants, and the expression of 6 lncRNA (PVT1, HOTAIR, MALAT1, NEAT1, GAS5, H19), selected from the literature, was quantified by RT-PCR and compared between the different groups. Statistical evaluation uncovered four lncRNAs with significantly distinct expression in Trial 1: PVT1 (LOG2FC = 1.194), GAS5 (LOG2FC = 0.8224), NEAT1 (LOG2FC = 1.497) and H19 (LOG2FC = −0.9958) and three lncRNA significantly different between TG and CG in Trial 2 (PVT1 (LOG2FC = −1.796), MALAT1 (LOG2FC = 2.834) and H19 (LOG2FC = 1.355). Among them, NEAT 1 stands aout as promissing diagnostic marker ans PVT1 and H19 may serve as both diagnosis and treatment monitoring, altough further validation in larger cohorts is needed to confirm these results.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 166-176"},"PeriodicalIF":5.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548779","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 : 2025-06-17DOI: 10.1016/j.ncrna.2025.06.002
Jia-Ning Zhang , Zi-Lu Yi , Xi-Rui Zhou , Sha-sha Liu , Hong Liu
Background
Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators in tumorigenesis and therapeutic resistance. This study investigates the prognostic significance and dual biological functions of lncRNA OTUD6B-AS1 in breast cancer (BC), focusing on its roles in immune evasion and ferroptosis resistance.
Methods
Multi-omics data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and lncRNA databases (AnnoLnc2, LncACTdb 3.0) were integrated to analyze OTUD6B-AS1 expression, clinical relevance, and molecular networks. Experimental validations included co-culture assays with CD8+ T cells, drug sensitivity tests, and ferroptosis marker analysis.
Results
OTUD6B-AS1 exhibited significant overexpression across multiple cancers, particularly in breast cancer (BC), where elevated levels strongly correlated with poor prognosis. Its expression was closely associated with key clinical indicators (T/N/M stage, ER/PR/HER2 status), prompting the development of a nomogram prognostic model with high clinical applicability. Genomic analysis revealed frequent amplification of OTUD6B-AS1 and co-occurrence of PIK3CA mutations. Co-expression and ceRNA networks highlighted its interaction with RNA degradation pathways. Notably, OTUD6B-AS1 was associated with immune evasion by regulating PD-L1 and CD8+ T cell activity. Concurrently, high OTUD6B-AS1 expression conferred ferroptosis resistance via GPX4/SLC7A11 modulation.
Conclusion
In conclusion, OTUD6B-AS1 serves as a biomarker in BC, driving immune evasion and ferroptosis resistance. Targeting OTUD6B-AS1 may enhance immunotherapy efficacy and overcome chemoresistance, offering novel therapeutic avenues.
{"title":"Dual role of lncRNA OTUD6B-AS1 in immune evasion and ferroptosis resistance: A prognostic and therapeutic biomarker in breast cancer","authors":"Jia-Ning Zhang , Zi-Lu Yi , Xi-Rui Zhou , Sha-sha Liu , Hong Liu","doi":"10.1016/j.ncrna.2025.06.002","DOIUrl":"10.1016/j.ncrna.2025.06.002","url":null,"abstract":"<div><h3>Background</h3><div>Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators in tumorigenesis and therapeutic resistance. This study investigates the prognostic significance and dual biological functions of lncRNA OTUD6B-AS1 in breast cancer (BC), focusing on its roles in immune evasion and ferroptosis resistance.</div></div><div><h3>Methods</h3><div>Multi-omics data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and lncRNA databases (AnnoLnc2, LncACTdb 3.0) were integrated to analyze OTUD6B-AS1 expression, clinical relevance, and molecular networks. Experimental validations included co-culture assays with CD8<sup>+</sup> T cells, drug sensitivity tests, and ferroptosis marker analysis.</div></div><div><h3>Results</h3><div>OTUD6B-AS1 exhibited significant overexpression across multiple cancers, particularly in breast cancer (BC), where elevated levels strongly correlated with poor prognosis. Its expression was closely associated with key clinical indicators (T/N/M stage, ER/PR/HER2 status), prompting the development of a nomogram prognostic model with high clinical applicability. Genomic analysis revealed frequent amplification of OTUD6B-AS1 and co-occurrence of PIK3CA mutations. Co-expression and ceRNA networks highlighted its interaction with RNA degradation pathways. Notably, OTUD6B-AS1 was associated with immune evasion by regulating PD-L1 and CD8<sup>+</sup> T cell activity. Concurrently, high OTUD6B-AS1 expression conferred ferroptosis resistance via GPX4/SLC7A11 modulation.</div></div><div><h3>Conclusion</h3><div>In conclusion, OTUD6B-AS1 serves as a biomarker in BC, driving immune evasion and ferroptosis resistance. Targeting OTUD6B-AS1 may enhance immunotherapy efficacy and overcome chemoresistance, offering novel therapeutic avenues.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 156-165"},"PeriodicalIF":5.9,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144489566","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 : 2025-06-09DOI: 10.1016/j.ncrna.2025.05.017
Tresa López-Royo , Laura Moreno-Martínez , Gabriel Rada , Sofía Macías-Redondo , Ana Cristina Calvo , Alberto García-Redondo , Raquel Manzano , Rosario Osta
Research in amyotrophic lateral sclerosis (ALS) faces major burdens, including the urgent need for sensitive and specific biomarkers, the identification of novel and effective therapeutic targets and a deeper understanding of the mechanisms driving the disease. In this line, long non-coding RNAs (lncRNAs) have emerged as promising candidates due to their regulatory role in a variety of important biological processes such as RNA metabolism, neuroinflammation, apoptosis or proteostasis.
This study aims to elucidate the expression profile of 14 lncRNAs in both the SOD1G93A mouse model and ALS patients. Different stages of the disease (presymptomatic, symptomatic and terminal) and 3 regions of the central nervous system (CNS) differentially affected by ALS (spinal cord, brainstem and frontal cortex) were included in the experimental design.
In SOD1G93A mice, all 14 lncRNAs exhibited differential expression patterns influenced by sex, age, and region, except for Malat1, Neat1, and H19, which displayed consistent expression patterns (Malat1 was decreased, while Neat1 and H19 were increased). These patterns were most prominent in the spinal cord, where lncRNAs were overall down-regulated. In contrast, in the brainstem and frontal cortex, lncRNAs were predominantly up-regulated. Notably, Gas5 expression levels in frontal cortex and spinal cord at the terminal stage correlated with the onset and progression of motor coordination and strength decline. Additionally, three lncRNAs (Gas5, Neat1 and Myoparr) were found to significantly correlate with survival.
In human ALS samples, increased levels of NEAT1 and SNHG16 were observed in the brainstem, and of MEG3 and H19 in the frontal cortex, whereas MALAT1 levels were decreased in frontal cortex.
In conclusion, this work supports lncRNAs as promising candidates as novel players and potential biomarkers in ALS and highlights SOD1G93A mice as a good model to study lncRNAs in the CNS in the context of this disease.
{"title":"LncRNA levels in the central nervous system as novel potential players and biomarkers in amyotrophic lateral sclerosis","authors":"Tresa López-Royo , Laura Moreno-Martínez , Gabriel Rada , Sofía Macías-Redondo , Ana Cristina Calvo , Alberto García-Redondo , Raquel Manzano , Rosario Osta","doi":"10.1016/j.ncrna.2025.05.017","DOIUrl":"10.1016/j.ncrna.2025.05.017","url":null,"abstract":"<div><div>Research in amyotrophic lateral sclerosis (ALS) faces major burdens, including the urgent need for sensitive and specific biomarkers, the identification of novel and effective therapeutic targets and a deeper understanding of the mechanisms driving the disease. In this line, long non-coding RNAs (lncRNAs) have emerged as promising candidates due to their regulatory role in a variety of important biological processes such as RNA metabolism, neuroinflammation, apoptosis or proteostasis.</div><div>This study aims to elucidate the expression profile of 14 lncRNAs in both the SOD1<sup>G93A</sup> mouse model and ALS patients. Different stages of the disease (presymptomatic, symptomatic and terminal) and 3 regions of the central nervous system (CNS) differentially affected by ALS (spinal cord, brainstem and frontal cortex) were included in the experimental design.</div><div>In SOD1<sup>G93A</sup> mice, all 14 lncRNAs exhibited differential expression patterns influenced by sex, age, and region, except for Malat1, Neat1, and H19, which displayed consistent expression patterns (Malat1 was decreased, while Neat1 and H19 were increased). These patterns were most prominent in the spinal cord, where lncRNAs were overall down-regulated. In contrast, in the brainstem and frontal cortex, lncRNAs were predominantly up-regulated. Notably, <em>Gas5</em> expression levels in frontal cortex and spinal cord at the terminal stage correlated with the onset and progression of motor coordination and strength decline. Additionally, three lncRNAs (<em>Gas5</em>, <em>Neat1</em> and <em>Myoparr</em>) were found to significantly correlate with survival.</div><div>In human ALS samples, increased levels of <em>NEAT1</em> and <em>SNHG16</em> were observed in the brainstem, and of <em>MEG3</em> and <em>H19</em> in the frontal cortex, whereas <em>MALAT1</em> levels were decreased in frontal cortex.</div><div>In conclusion, this work supports lncRNAs as promising candidates as novel players and potential biomarkers in ALS and highlights SOD1<sup>G93A</sup> mice as a good model to study lncRNAs in the CNS in the context of this disease.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 145-155"},"PeriodicalIF":5.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471691","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}
Long noncoding RNAs (lncRNAs) play crucial roles in the progression of human malignancies; however, their involvement in esophageal cancer (ESCA) remains incompletely understood. In this study, we screened for lncRNAs upregulated in ESCA and identified 12 lncRNAs significantly upregulated in primary ESCA tumors. Among those, elevated LINC02154 expression correlated positively with advanced T stages. LINC02154 knockdown in ESCA cell lines suppressed cell proliferation and migration, while ectopic expression of LINC02154 enhanced colony formation. Depletion of LINC02154 suppressed genes involved in various oncogenic processes, including cell cycling, epithelial-mesenchymal transition (EMT), and metabolism. We also found that LINC02154 promotes EMT and enhances chemoresistance, at least in part, through suppression of miR-200b. Finally, RNA-pulldown and mass spectrometry analysis revealed that LINC02154 interacts with proteins involved in the cornified envelope or desmosome. These findings suggest that LINC02154 exerts oncogenic effects through modulation of multiple oncogenic signaling pathways in ESCA and that LINC02154 is a potential therapeutic target.
{"title":"Upregulation of LINC02154 promotes esophageal cancer progression by enhancing cell cycling and epithelial-mesenchymal transition","authors":"Kotoha Shimote , Takeshi Niinuma , Hiroshi Kitajima , Kazuya Ishiguro , Eiichiro Yamamoto , Gota Sudo , Akira Yorozu , Mutsumi Toyota , Masahiro Kai , Masashi Idogawa , Hiromu Suzuki","doi":"10.1016/j.ncrna.2025.06.001","DOIUrl":"10.1016/j.ncrna.2025.06.001","url":null,"abstract":"<div><div>Long noncoding RNAs (lncRNAs) play crucial roles in the progression of human malignancies; however, their involvement in esophageal cancer (ESCA) remains incompletely understood. In this study, we screened for lncRNAs upregulated in ESCA and identified 12 lncRNAs significantly upregulated in primary ESCA tumors. Among those, elevated LINC02154 expression correlated positively with advanced T stages. LINC02154 knockdown in ESCA cell lines suppressed cell proliferation and migration, while ectopic expression of LINC02154 enhanced colony formation. Depletion of LINC02154 suppressed genes involved in various oncogenic processes, including cell cycling, epithelial-mesenchymal transition (EMT), and metabolism. We also found that LINC02154 promotes EMT and enhances chemoresistance, at least in part, through suppression of miR-200b. Finally, RNA-pulldown and mass spectrometry analysis revealed that LINC02154 interacts with proteins involved in the cornified envelope or desmosome. These findings suggest that LINC02154 exerts oncogenic effects through modulation of multiple oncogenic signaling pathways in ESCA and that LINC02154 is a potential therapeutic target.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 107-116"},"PeriodicalIF":5.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231637","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 : 2025-05-30DOI: 10.1016/j.ncrna.2025.05.015
Yang Wang , Cong Wang , Xin Dai , Ge Liu , Xiaolong Gao , Junru Zhang
Aging is an inevitable physiological process that occurs in living organisms and has significant implications for health and disease. As the human lifespan extends, the functionality of organs gradually diminishes, leading to the emergence of various aging-related symptoms. While it is not feasible to completely halt the aging process, investigating key molecules involved in aging can help devise valid strategies to delay its progression. Circular RNAs (circRNAs) are a novel category of non-protein-coding RNAs and are abundant in cells. Their distinctive circular structure and diverse biological functions have garnered considerable attention from the scientific community. CircRNAs play a crucial role in regulating biological processes such as the cell cycle, apoptosis, and autophagy. They are implicated in various mechanisms, including cell signaling, influencing post-transcriptional regulation, and functioning as sponges for microRNAs (miRNAs), to modulate gene expression and impact cellular senescence. This research paper sets out to elucidate the mechanisms by which circRNAs regulate gene expression, epigenetic modifications, and cellular functions, as well as to assess their potential applications in aging-associated disorders.
{"title":"Deciphering the multifaceted role of circular RNA in aging: from molecular mechanisms to therapeutic potentials","authors":"Yang Wang , Cong Wang , Xin Dai , Ge Liu , Xiaolong Gao , Junru Zhang","doi":"10.1016/j.ncrna.2025.05.015","DOIUrl":"10.1016/j.ncrna.2025.05.015","url":null,"abstract":"<div><div>Aging is an inevitable physiological process that occurs in living organisms and has significant implications for health and disease. As the human lifespan extends, the functionality of organs gradually diminishes, leading to the emergence of various aging-related symptoms. While it is not feasible to completely halt the aging process, investigating key molecules involved in aging can help devise valid strategies to delay its progression. Circular RNAs (circRNAs) are a novel category of non-protein-coding RNAs and are abundant in cells. Their distinctive circular structure and diverse biological functions have garnered considerable attention from the scientific community. CircRNAs play a crucial role in regulating biological processes such as the cell cycle, apoptosis, and autophagy. They are implicated in various mechanisms, including cell signaling, influencing post-transcriptional regulation, and functioning as sponges for microRNAs (miRNAs), to modulate gene expression and impact cellular senescence. This research paper sets out to elucidate the mechanisms by which circRNAs regulate gene expression, epigenetic modifications, and cellular functions, as well as to assess their potential applications in aging-associated disorders.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 129-144"},"PeriodicalIF":5.9,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144254875","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 : 2025-05-28DOI: 10.1016/j.ncrna.2025.05.014
Gusai Elhassan , Xiangxue Bu , Jiaxin Liu , Shuai Hou , Jinsong Yan , Haixin Lei
Loss or decreased expression of lncRNA MEG3 is a frequent event in the progression of many different malignancies. Overexpression of MEG3 in breast cancer cell lines MCF7 or MDA-MB-231 prevented cell migration, whereas depletion of MEG3 in human mammary epithelial cell line MCF10A strikingly promoted cell migration. As RNA-protein interactions are vital for RNA to function, RNP assembled on MEG3 in vivo was purified using affinity purification followed by mass spectrometry, which revealed ∼600 proteins with the potential to interact with MEG3. Bioinformatic analysis on RNA-seq data from MCF7 with MEG3 overexpression and MCF10A with MEG3 depletion led to the identification of CXCR4 as the major downstream mediator negatively regulated by MEG3 that facilitated breast cancer cell migration. In addition, the chromatin regulator CTCF emerged as the MEG3-binding protein that might regulate CXCR4 expression after comparison of proteins presenting in MEG3 lncRNP to ChIP-seq data and GPSAdb data of CXCR4. Further evidence was provided to show CTCF upregulated the expression of CXCR4 at transcriptional level, whereas co-expression of MEG3 with CTCF abolished transcriptional activation of CXCR4. Overall, our study pinpoints the importance of MEG3/CTCF-CXCR4 axis in regulating migration of breast cancer cells and provides novel insight into the mechanism of lncRNA MEG3 in cancer development.
{"title":"LncRNA MEG3/CTCF-CXCR4 axis functions in the regulation of breast cancer cell migration","authors":"Gusai Elhassan , Xiangxue Bu , Jiaxin Liu , Shuai Hou , Jinsong Yan , Haixin Lei","doi":"10.1016/j.ncrna.2025.05.014","DOIUrl":"10.1016/j.ncrna.2025.05.014","url":null,"abstract":"<div><div>Loss or decreased expression of lncRNA MEG3 is a frequent event in the progression of many different malignancies. Overexpression of MEG3 in breast cancer cell lines MCF7 or MDA-MB-231 prevented cell migration, whereas depletion of MEG3 in human mammary epithelial cell line MCF10A strikingly promoted cell migration. As RNA-protein interactions are vital for RNA to function, RNP assembled on MEG3 <em>in vivo</em> was purified using affinity purification followed by mass spectrometry, which revealed ∼600 proteins with the potential to interact with MEG3. Bioinformatic analysis on RNA-seq data from MCF7 with MEG3 overexpression and MCF10A with MEG3 depletion led to the identification of CXCR4 as the major downstream mediator negatively regulated by MEG3 that facilitated breast cancer cell migration. In addition, the chromatin regulator CTCF emerged as the MEG3-binding protein that might regulate CXCR4 expression after comparison of proteins presenting in MEG3 lncRNP to ChIP-seq data and GPSAdb data of CXCR4. Further evidence was provided to show CTCF upregulated the expression of CXCR4 at transcriptional level, whereas co-expression of MEG3 with CTCF abolished transcriptional activation of CXCR4. Overall, our study pinpoints the importance of MEG3/CTCF-CXCR4 axis in regulating migration of breast cancer cells and provides novel insight into the mechanism of lncRNA MEG3 in cancer development.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 117-128"},"PeriodicalIF":5.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241990","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 : 2025-05-28DOI: 10.1016/j.ncrna.2025.05.016
Chang-Luo Li , Jin-Kun Zhuang , Zhong Liu , Zhong-Run Huang , Chun Xiang , Qian-Yu Chen , Ze-Xin Chen , Zhong-Song Shi
Background
Hemorrhage transformation (HT) following endovascular reperfusion treatment is associated with worse clinical outcomes in acute ischemic stroke patients. MicroRNA (miR) modulates several aspects of cerebral ischemia-reperfusion injury, including blood-brain barrier (BBB) integrity, inflammation, oxidative stress, and apoptosis, significantly impacting cerebral recovery and function. This study investigated the role of astrocytic miR-29a-5p in HT in the transient middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation reoxygenation (OGD/R) model of astrocytes.
Methods
MiR-29a-5p expression in the OGD/R astrocyte model was assessed. The astrocyte injury, the expression of A1 and A2 phenotypes of reactive astrocytes, and the regulation of miR-29a-5p target genes were evaluated after the miR-29a-5p intervention. A mechanical reperfusion-induced HT model was established in hyperglycemic rats using 5-h MCAO following reperfusion at 6 h. MiR-29a-5p agomir was administered intravenously before reperfusion. Infarct volume, HT, BBB damage, neurological score, the expression of miR-29a-5p, and its target genes were evaluated.
Results
MiR-29a-5p expression decreased in OGD/R-treated astrocytes and the peri-infarction tissue and blood of the MCAO model. Elevating miR-29a-5p levels reduced astrocyte injury, suppressed neurotoxic A1 astrocyte markers (C3, Fkbp5, and Serping1), while enhanced neuroprotective A2 astrocyte markers (S100a10 and Emp1) in the OGD/R and MCAO models. Intravenous administration of miR-29a-5p agomir increased the expression of miR-29a-5p and reduced infarct volume, reperfusion-induced HT, and BBB breakdown after ischemia, improving neurological outcomes in the MCAO model. Overexpression of miR-29a-5p effectively suppressed the expression of its direct target genes, glycogen synthase kinase 3 beta and aquaporin 4 in the OGD/R and MCAO models.
Conclusions
MiR-29a-5p alleviates astrocyte injury and regulates A1 and A2 astrocyte markers, glycogen synthase kinase 3 beta, and aquaporin 4 in astrocytes subjected to ischemia-reperfusion injury. Astrocytic miR-29a-5p may be a protective target for reducing HT and improving outcomes following mechanical reperfusion in acute ischemic stroke.
{"title":"MicroRNA-29a-5p attenuates hemorrhagic transformation and improves outcomes after mechanical reperfusion for acute ischemic stroke","authors":"Chang-Luo Li , Jin-Kun Zhuang , Zhong Liu , Zhong-Run Huang , Chun Xiang , Qian-Yu Chen , Ze-Xin Chen , Zhong-Song Shi","doi":"10.1016/j.ncrna.2025.05.016","DOIUrl":"10.1016/j.ncrna.2025.05.016","url":null,"abstract":"<div><h3>Background</h3><div>Hemorrhage transformation (HT) following endovascular reperfusion treatment is associated with worse clinical outcomes in acute ischemic stroke patients. MicroRNA (miR) modulates several aspects of cerebral ischemia-reperfusion injury, including blood-brain barrier (BBB) integrity, inflammation, oxidative stress, and apoptosis, significantly impacting cerebral recovery and function. This study investigated the role of astrocytic miR-29a-5p in HT in the transient middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation reoxygenation (OGD/R) model of astrocytes.</div></div><div><h3>Methods</h3><div>MiR-29a-5p expression in the OGD/R astrocyte model was assessed. The astrocyte injury, the expression of A1 and A2 phenotypes of reactive astrocytes, and the regulation of miR-29a-5p target genes were evaluated after the miR-29a-5p intervention. A mechanical reperfusion-induced HT model was established in hyperglycemic rats using 5-h MCAO following reperfusion at 6 h. MiR-29a-5p agomir was administered intravenously before reperfusion. Infarct volume, HT, BBB damage, neurological score, the expression of miR-29a-5p, and its target genes were evaluated.</div></div><div><h3>Results</h3><div>MiR-29a-5p expression decreased in OGD/R-treated astrocytes and the peri-infarction tissue and blood of the MCAO model. Elevating miR-29a-5p levels reduced astrocyte injury, suppressed neurotoxic A1 astrocyte markers (C3, Fkbp5, and Serping1), while enhanced neuroprotective A2 astrocyte markers (S100a10 and Emp1) in the OGD/R and MCAO models. Intravenous administration of miR-29a-5p agomir increased the expression of miR-29a-5p and reduced infarct volume, reperfusion-induced HT, and BBB breakdown after ischemia, improving neurological outcomes in the MCAO model. Overexpression of miR-29a-5p effectively suppressed the expression of its direct target genes, glycogen synthase kinase 3 beta and aquaporin 4 in the OGD/R and MCAO models.</div></div><div><h3>Conclusions</h3><div>MiR-29a-5p alleviates astrocyte injury and regulates A1 and A2 astrocyte markers, glycogen synthase kinase 3 beta, and aquaporin 4 in astrocytes subjected to ischemia-reperfusion injury. Astrocytic miR-29a-5p may be a protective target for reducing HT and improving outcomes following mechanical reperfusion in acute ischemic stroke.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 96-106"},"PeriodicalIF":5.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231636","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号