Non-coding RNA Research最新文献

{"title":"Stability of microRNAs in serum and plasma reveal promise as a circulating biomarker","authors":"Erryk S. Katayama ,&nbsp;Jonathan J. Hue ,&nbsp;Alexander W. Loftus ,&nbsp;Semmer A. Ali ,&nbsp;Hallie J. Graor ,&nbsp;Luke D. Rothermel ,&nbsp;Eric Londin ,&nbsp;Mehrdad Zarei ,&nbsp;Jordan M. Winter","doi":"10.1016/j.ncrna.2025.08.001","DOIUrl":"10.1016/j.ncrna.2025.08.001","url":null,"abstract":"<div><h3>Purpose</h3><div>To verify the stability and reliability of circulating microRNA (miRNA) profiles in plasma and serum under different processing and storage conditions to inform future applications to circulating biomarker analyses.</div></div><div><h3>Background</h3><div>The development of blood-based methods for early disease detection has become increasingly desirable across various medical fields. RNA profiles have been investigated but have been a challenge due to rapid degradation of the analyte by ubiquitous RNases. miRNAs are short, non-coding regulatory RNAs that are believed to be more stable under certain conditions, large in number, and specific to cell type and disease state. Thus, circulating miRNA profiles hold significant promise as diagnostic biomarkers for a range of conditions, including cancer, autoimmune, liver, neurological, metabolic, and cardiovascular diseases. However, to realize their full potential in clinical applications, it is crucial to thoroughly characterize the stability of miRNAs under various blood collection, processing, and storage conditions prior to their investigation and large-scale application in disease-specific biomarker discovery studies.</div></div><div><h3>Methods</h3><div>Plasma or serum were extracted from whole blood of healthy volunteers. Samples were stored at different temperatures (4 °C or 25 °C, room temperature) for varying periods (0–24 h) to mimic possible delays in processing encountered in routine clinical settings. miRNA was extracted and profiles were assessed with RT-qPCR or small RNA-sequencing techniques.</div></div><div><h3>Results</h3><div>Mean Cq values of specific miRNAs, such as miR-15b, miR-16, miR-21, miR-24, and miR-223, remained consistent between 0 and 24 h when serum and plasma were stored on ice. Minimal changes were observed in mean Cq values over 24 h when serum was left at room temperature as well. Similar trends were observed when miRNAs from plasma were analyzed. Small-RNA sequencing detected approximately ∼650 different miRNA signals in plasma, with over 99 % of the miRNA profile unchanged even when blood draw tubes were left at room temperature for 6 h prior to processing.</div></div><div><h3>Conclusions</h3><div>These data demonstrate remarkable stability of miRNAs over time, which should withstand variability in handling and processing that can occur with routine clinical lab draws. Considering the large diversity of miRNAs, this analyte class should be thoroughly investigated as a non-invasive biomarker of diverse disease states.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"15 ","pages":"Pages 132-141"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144920242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AutoML identification of microRNA biomarkers in high-risk pediatric acute lymphoblastic leukemia","authors":"Ioannis Kyriakidis ,&nbsp;Zacharias Papadovasilakis ,&nbsp;Georgios Papoutsoglou ,&nbsp;Iordanis Pelagiadis ,&nbsp;Helen A. Papadaki ,&nbsp;Charalampos Pontikoglou ,&nbsp;Eftichia Stiakaki","doi":"10.1016/j.ncrna.2025.08.003","DOIUrl":"10.1016/j.ncrna.2025.08.003","url":null,"abstract":"<div><div>Despite significant advancements in overall survival rates for childhood acute lymphoblastic leukemia (ALL), relapse continues to pose a major challenge. MicroRNAs have proven valuable for improving diagnosis, treatment, and survival outcomes, establishing themselves as key biomarkers. Using RNA-seq data from 123 ALL patients and employing predictive modeling via automated machine learning (AutoML) alongside causal-inspired biomarker discovery, we identified highly predictive microRNA signatures linked to high-risk strata and clinical features in unfavorable cases. We further identified predictive signatures for each genetic subtype of childhood ALL, highlighting shared miRNAs throughout the study. A thorough literature review of the relationships between miRNA differential expression and key high-risk features in childhood ALL [immunophenotype, elevated white blood cell counts at diagnosis, central nervous system involvement, measurable residual disease (MRD), and chemoresistance] confirmed the signatures generated in this study. Our results revealed a highly predictive signature distinguishing B- and T-ALL, associated with apoptosis, confirming the reported difference between the two immunophenotypes. Additionally, miR-223 emerged as crucial for high-risk stratification and chemoresistant MRD-positive cases. These findings demonstrate the potential of AutoML tools to reveal novel biological insights in pediatric ALL, driving future advancements.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"15 ","pages":"Pages 120-131"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mechanism 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 ,&nbsp;Nan Wang ,&nbsp;Jinying Hu,&nbsp;Minlan Luo,&nbsp;Na Zhang,&nbsp;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":"2025-12-01","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}

{"title":"Serum lncRNAs NEAT1, PVT1 and H19 as novel biomarkers for sarcopenia diagnosis and treatment response","authors":"Paula Aparicio ,&nbsp;Tresa López-Royo ,&nbsp;David Navarrete-Villanueva ,&nbsp;Alba María Gómez Cabello ,&nbsp;Marcela González-Gross ,&nbsp;Ignacio Ara ,&nbsp;Germán Vicente-Rodríguez ,&nbsp;Rosario Osta ,&nbsp;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":"2025-10-01","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}

{"title":"Exosome-derived hsa_circ_0007132 promotes lenvatinib resistance by inhibiting the ubiquitin-mediated degradation of NONO","authors":"Mingbo Cao ,&nbsp;Yuxuan Li ,&nbsp;Xiaorui Su ,&nbsp;Yongchang Tang ,&nbsp;Feng Yuan ,&nbsp;Yupeng Ren ,&nbsp;Meihai Deng ,&nbsp;Zhicheng Yao","doi":"10.1016/j.ncrna.2025.05.007","DOIUrl":"10.1016/j.ncrna.2025.05.007","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a highly heterogeneous solid tumor, with its incidence showing a troubling upward trend over the past decade. Lenvatinib is one of the first-line medications for treating advanced HCC, however, the development of resistance significantly undermines its potential to improve patient prognosis. In recent years, exosomal circRNAs have been implicated in the resistance mechanisms of various cancers, yet their role in mediating lenvatinib resistance (LR) remains largely unexplored. In this study, we identified hsa_circ_0007132, which is upregulated in the serum exosomes of HCC patients exhibiting progressive disease (PD) following lenvatinib treatment. Subsequently, we employed LR cell lines to conduct both <em>in vitro</em> and <em>in vivo</em> experiments, which provided compelling evidence that hsa_circ_0007132 significantly promotes LR in HCC. Mechanistically, hsa_circ_0007132 interacts with the NONO protein, impairing its ubiquitination and leading to increased stability and upregulation of NONO expression, thereby enhancing NONO-mediated nuclear export of ZEB1 mRNA and elevating ZEB1 protein expression, which ultimately contributes to LR. In summary, our findings unveil a critical mechanism through which HCC mediates tumor progression and LR via exosomal hsa_circ_0007132, while also emphasizing that targeting NONO may represent a promising therapeutic strategy to overcome LR.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 1-13"},"PeriodicalIF":5.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NSUN2-mediated m5C hypermethylation of hsa_circ_0004516 promotes breast cancer brain metastasis by activating AKT signaling","authors":"Min Li ,&nbsp;Jiawei Li ,&nbsp;Hongbo Wen ,&nbsp;Jun Li ,&nbsp;Song Wang ,&nbsp;Jianran Guo ,&nbsp;Dongyan Zhang ,&nbsp;Anqi Zhang ,&nbsp;Chuanyou Cui ,&nbsp;Rong Fu ,&nbsp;Meng An ,&nbsp;Wei Zhang ,&nbsp;Bo Fu","doi":"10.1016/j.ncrna.2025.08.009","DOIUrl":"10.1016/j.ncrna.2025.08.009","url":null,"abstract":"<div><div>Breast cancer brain metastasis (BCBM) remains fatal with elusive mechanisms. Here, we unveil the first circRNA m5C methylation landscape in BCBM through MeRIP-seq (methylated RNA immunoprecipitation next-generation sequencing) identifying 7465 BCBM-specific m5C peaks versus 5929 in primary breast cancer (BC). A total of 48 hypermethylated and 128 hypomethylated m5C sites in BCBM (231-BR) were identified compared to BC. Bioinformatics enrichment analysis revealed hypermethylated circRNAs enriched in ERBB/VEGF signaling pathways. Among 8 validated differentially methylated circRNAs, <em>hsa_circ_0004516</em> was consistently upregulated in BCBM tissues/cells and exhibited NSUN2-dependent m5C modification. Mechanistically, NSUN2-mediated m5C methylation enhanced <em>hsa_circ_0004516</em> stability, evidenced by significantly shortened half-life upon NSUN2 depletion. Crucially, catalytic mutant NSUN2 (C271A/C321A) abolished this effect. Functional assays demonstrated that <em>hsa_circ_0004516</em> knockdown in 231-BR cells suppressed proliferation, migration, and invasion by reducing p-AKT (Ser473) levels. The AKT activator SC79 reversed these phenotypic impairments, definitively linking <em>hsa_circ_0004516</em>-driven metastasis to AKT signaling activation. Our study establishes the NSUN2-m5C-<em>hsa_circ_</em>0004516-AKT axis as a novel therapeutic target and biomarker for BCBM.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 177-190"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncPTEN1, a long non-coding RNA generated from PTEN, suppresses lung cancer metastasis through the regulation of EMT progress","authors":"Zichu Shen ,&nbsp;Ailin Zhong ,&nbsp;Chun Zhang ,&nbsp;Xiaowei Tang ,&nbsp;Xuyang Zhao ,&nbsp;Zhiyuan Hou ,&nbsp;Hui Liang ,&nbsp;Yuxin Yin","doi":"10.1016/j.ncrna.2025.05.011","DOIUrl":"10.1016/j.ncrna.2025.05.011","url":null,"abstract":"<div><div>Lung cancer is among the most frequently observed and lethal malignancies globally, and metastasis represents a critical determinant of patient outcomes. PTEN, a well-established tumor suppressor, has emerged as an important regulator in lung cancer progression. However, the molecular mechanism of <em>PTEN</em> gene suppressing lung cancer metastasis lacks deeper exploration. In this research, we identify and characterize LncPTEN1, a novel long non-coding RNA generated from <em>PTEN</em> gene. We show that YTHDC1 promotes the alternative splicing of LncPTEN1, resulting in significantly elevated LncPTEN1 expression in normal lung cells. Clinical analyses across multiple patient cohorts demonstrate that low LncPTEN1 expression strongly correlates with poor patient survival and increased metastasis, indicating its potential as a prognostic biomarker. Mechanistically, LncPTEN1 facilitates the interaction between Trim16 and Vimentin, promoting the ubiquitination and proteasomal degradation of Vimentin, thereby suppressing EMT-driven metastasis. The collective evidence from our investigation demonstrates that LncPTEN1 represents a novel tumor-suppressive lncRNA which inhibits lung cancer metastasis through promoting the degradation of Vimentin and inhibiting the EMT progress.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 25-37"},"PeriodicalIF":5.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alternative transcription increases isoform complexity in Long Non-Coding RNAs and alters their functions in cancer","authors":"Max Bone ,&nbsp;Gareth J. Inman","doi":"10.1016/j.ncrna.2025.04.008","DOIUrl":"10.1016/j.ncrna.2025.04.008","url":null,"abstract":"<div><div>Transcriptional start and end variance, a less-explored aspect of lncRNA biology, is a critical determinant of isoform diversity in human RNA. While alternative splicing (AS) has been extensively studied as a mechanism of isoform generation, differences in transcriptional start and termination site usage—whether from distinct promoters or varying initiation events at the same core promoter—contribute more to isoform diversity than alternative splicing. In the context of long non-coding RNAs (lncRNAs), even subtle alterations to transcriptional start and end sites can induce significant changes in the structural and functional capacities of individual lncRNA isoforms.</div><div>This review highlights the underappreciated realm of transcriptional start and end variance in lncRNAs, exploring its pivotal role in shaping the diversity of lncRNA transcripts. In cancer, where lncRNAs are increasingly recognised as key players in tumorigenesis, understanding the ramifications of transcriptional start and end variance is crucial. With single nucleotide alterations capable of influencing the folding energy, shape, stability, and function of a lncRNA molecules, significant changes to transcriptional regulation may lead to aberrant isoforms with implications for cancer initiation, progression, and potentially, its treatment.</div><div>As lncRNAs emerge as therapeutic targets, particularly with the advancement of antisense oligonucleotide (ASO) technologies, it becomes crucial to understand the regulatory landscape of transcriptional variation among lncRNA isoforms, to ensure selective targeting of oncogenic transcripts while sparing those with normal physiological functions. By highlighting the significance of transcriptional start and end site variation as major contributors to lncRNA diversity, the potential exploitation for precision therapeutic interventions in the field of non-coding RNA cancer research can be expanded.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 38-50"},"PeriodicalIF":5.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-92a-1-5p contributes to cellular proliferation and survival in chronic myeloid leukemia and its inhibition enhances imatinib efficacy","authors":"Joanne Peters ,&nbsp;Emeline Bollaert ,&nbsp;Anne-Sophie Cloos ,&nbsp;Melissa Claus ,&nbsp;Ahmed Essaghir ,&nbsp;Sandrine Lenglez ,&nbsp;Pascale Saussoy ,&nbsp;Guillaume Dachy ,&nbsp;Pierre Autin ,&nbsp;Jean-Baptiste Demoulin ,&nbsp;Violaine Havelange","doi":"10.1016/j.ncrna.2025.05.008","DOIUrl":"10.1016/j.ncrna.2025.05.008","url":null,"abstract":"<div><div>Tyrosine kinase inhibitors (TKI), such as imatinib, have revolutionized chronic myeloid leukemia (CML) treatment. Despite this success, TKI intolerance and resistance remain significant clinical challenges. A promising therapeutic approach is to simultaneously target the <em>BCR::ABL1</em> oncogene and other oncogenic drivers. The polycistronic <em>miR-17-92</em> cluster is known to contribute to CML development and progression, but the specific roles of <em>miR-92a-1-5p</em> within this cluster remain unclear. In this study, we assess the roles of this microRNA and evaluate the therapeutic potential of combining microRNA inhibition with imatinib to improve treatment outcome. Our results show that <em>miR-92a-1-5p</em> is downregulated by imatinib in myeloid cell lines harboring <em>BCR::ABL1</em> and in CML patient samples. Inhibition of <em>miR-92a-1-5p</em> reduces proliferation and enhances imatinib-induced cell death, while its overexpression increases proliferation and counteracts the effects of imatinib on cell death. This decrease in proliferation caused by <em>miR-92a-1-5p</em> inhibition is rescued after simultaneous inhibition of two newly identified target genes: <em>BNIP3L (NIX)</em> and <em>TP53INP1</em>. We confirm that <em>miR-92a-1-5p</em> regulates proliferation and cell cycle by targeting <em>TP53INP1</em> and decreases autophagy by targeting <em>BNIP3L</em>. Our data suggest that <em>miR-92a-1-5p</em> plays a role in CML progression, and its inhibition enhances imatinib anti-leukemic efficacy, making it a potential therapeutic target.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 14-24"},"PeriodicalIF":5.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual role of lncRNA OTUD6B-AS1 in immune evasion and ferroptosis resistance: A prognostic and therapeutic biomarker in breast cancer","authors":"Jia-Ning Zhang ,&nbsp;Zi-Lu Yi ,&nbsp;Xi-Rui Zhou ,&nbsp;Sha-sha Liu ,&nbsp;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⁺ 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⁺ 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":"2025-10-01","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}