Non-Coding RNA最新文献

{"title":"Exploratory Machine Learning Analysis of circRNA-Derived Molecular Features in Autism Spectrum Disorder.","authors":"Raunak Sharda, Valentina L Kouznetsova, Igor F Tsigelny","doi":"10.3390/ncrna12030017","DOIUrl":"10.3390/ncrna12030017","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Autism Spectrum Disorder (ASD) is a set of neurological and neurodevelopmental disorders characterized by difficulties in social communication and interaction, repetitive behaviors, and sensory processing differences. Recent studies have shown that circRNAs play a crucial role in the pathophysiology of ASD. In this study, we present an exploratory machine learning framework integrating circRNA sequence features, miRNA interactions, gene targets, and pathway enrichment analysis to investigate ASD-associated molecular signatures. <b>Methods:</b> Differential circRNAs were identified from human peripheral blood datasets, and informative features were selected using attribute-based filtering and Information Gain ranking. Machine learning models were developed using the WEKA platform. <b>Results:</b> The HyperPipes classifier achieved the highest performance (92.5% accuracy under cross-validation). Analysis using an independent ASD gene expression dataset showed consistent discriminative patterns of the derived gene-level signatures across multiple machine learning classifiers. The competitive endogenous RNA network and enriched gene pathways were also analyzed. <b>Conclusions:</b> Overall, this study provides a computational, preliminary framework for analyzing circRNA-associated molecular patterns in ASD. Findings should be interpreted in the context of limited sample size and dataset availability.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"12 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148033601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urinary Exosomal microRNAs as a Novel Approach to Study People with Multiple Sclerosis and Severe Gait Disability: A Preliminary Observation.","authors":"Silvia Grassilli, Andrea Baroni, Marina Pierantoni, Federica Brugnoli, Nicola Lamberti, Sofia Straudi, Fabio Manfredini, Valeria Bertagnolo","doi":"10.3390/ncrna12030016","DOIUrl":"10.3390/ncrna12030016","url":null,"abstract":"<p><p><b>Background:</b> MiRNAs within extracellular vesicles can encompass body barriers, reflecting stage, progression, and response to treatments of various diseases, including multiple sclerosis (MS)-a chronic immune-mediated disease of the central nervous system that causes progressive disability, with highly variable clinical courses. In this context, urinary exosomal miRNAs could be an appealing source of biomarkers, thanks to their non-invasive and easily repeatable collection. <b>Methods:</b> In this exploratory investigation, we tried to assess if profiling urinary exosomal miRNAs could reveal subtle differences within an apparently homogeneous MS population. The study involved 24 patients with primary or secondary progressive MS, whose urinary exosomes (UEs) were subjected to evaluation of a panel of 87 miRNAs variously correlated with neuroinflammation, cardiovascular functions, and/or involved in MS. <b>Results:</b> We revealed that the examined miRNAs were heterogeneously expressed across the patients, reflecting, as expected, their gender and/or hormonal status. Two miRNAs discriminated against primary or secondary progressive MS, and a panel of 14 commonly upmodulated miRNAs identified patients with longer disease duration and a greater degree of disability. <b>Conclusions:</b> Even if preliminary, these data represent the first relationship between UEs and MS features in humans and suggest that urine could constitute a non-invasive source of exosomal miRNAs, which could prove useful in complementing conventional monitoring to provide a more personalized management of MS patients.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"12 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148033650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hnf1aos1 as a Metabolic Coordinator of Hepatic Lipid Homeostasis and Feedback Control.","authors":"Beshoy Armanios, Jing Jin, Ankit P Laddha, Le Tra Giang Nguyen, Sherouk M Tawfik, Neha Mishra, Jose E Manautou, Xiao-Bo Zhong","doi":"10.3390/ncrna12030015","DOIUrl":"10.3390/ncrna12030015","url":null,"abstract":"<p><p><b>Background:</b> Long noncoding RNAs (lncRNAs) have emerged as critical regulators of hepatic metabolism and disease progression. The hepatocyte nuclear factor 1 alpha antisense 1 (HNF1A-AS1) lncRNA modulates liver-specific transcription factors; however, its physiological role in diet-dependent lipid homeostasis remains poorly defined. <b>Methods:</b> In this study, we investigated the mouse ortholog, Hnf1a opposite strand 1 (Hnf1aos1), using AAV-mediated knockdown in C57BL/6J mice fed either a chow diet (10% kcal from fat) or a high-fat diet (HFD; 60% kcal from fat) for 12 weeks. Metabolic phenotyping included hepatic lipid quantification, histological analysis, serum biochemistry, and quantitative gene expression profiling. <b>Results:</b> Loss of Hnf1aos1 produced distinct, diet-dependent alterations in hepatic lipid handling. Under chow conditions, knockdown mice exhibited selective hepatic cholesterol accumulation (6.10 ± 2.9 mg/g tissue vs. 3.51 ± 1.1 mg/g in controls), accompanied by dysregulation of cholesterol clearance pathways. In contrast, under HFD conditions, knockdown precipitated severe macrovesicular degeneration, with hepatic triglyceride levels approximately doubled relative to HFD-fed controls (51.72 ± 19.8 mg/g vs. 26.34 ± 11.9 mg/g) and a numerically elevated triglyceride-to-cholesterol ratio (TG:TC ≈ 6.1:1; <i>p</i> = 0.0621, trend). Chow/Kd mice gained significantly less weight than chow-fed controls, whereas HFD/Kd mice exhibited weight gain comparable to HFD controls despite severe hepatic steatosis. This paradoxical phenotype suggests impaired metabolic feedback at the post-transcriptional level, in which compensatory upregulation of <i>Hnf1a</i> mRNA is insufficient to suppress lipid-associated genes such as Cd36, despite profound lipid overload; however, HNF1A protein levels were not directly measured in this study. <b>Conclusion:</b> Collectively, these findings identify Hnf1aos1 as a regulator of hepatic lipid homeostasis whose loss produces a phenotype consistent with inappropriate lipid accumulation during nutrient excess, without defining the underlying molecular mechanism. Our results support a role for Hnf1aos1 in shaping hepatic metabolic plasticity and provide insight into lncRNA-associated MASLD phenotypes.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"12 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148033581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circular RNAs in Intestinal Mucosal Homeostasis and Pathologies.","authors":"Hee Kyoung Chung, Lan Xiao, Jian-Ying Wang","doi":"10.3390/ncrna12030014","DOIUrl":"10.3390/ncrna12030014","url":null,"abstract":"<p><p>The mammalian intestinal epithelium is a rapid self-renewal tissue in the body, serving as a critical interface between the host and the external environment. Maintaining the intestinal epithelium homeostasis requires precise coordination of cellular processes, including proliferation, migration, differentiation, autophagy, and cell-to-cell interaction. An increasing body of evidence has unveiled circular RNAs (circRNAs) as abundant and stable regulatory molecules that play pivotal roles in the intestinal epithelial biology and are intimately involved in many aspects of gut mucosal pathologies. Unlike linear RNAs, circRNAs form covalently closed loop structures through back-splicing events, conferring remarkable stability and resistance to exonucleolytic degradation. circRNAs regulate the growth of the intestinal mucosa, injury-induced epithelial regeneration, and gut barrier function via diverse mechanisms, including interactions with microRNAs and RNA-binding proteins. Deregulated circRNAs are implicated in the pathogenesis of various gut mucosal disorders such as inflammatory bowel disease and malignancies. In this review, we highlight pathobiological functions and mechanisms of intestinal epithelium-enriched circRNAs, particularly <i>circHIPK3</i>, <i>Cdrlas</i>, and <i>circPABPN1</i>, in the epithelium homeostasis and pathologies and also discuss potential clinical application of circRNAs as diagnostic biomarkers and therapeutic targets in patients with critical diseases.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"12 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148033617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropathic Pain: Mapping the miRNA Landscape.","authors":"Mario García-Domínguez","doi":"10.3390/ncrna12020013","DOIUrl":"10.3390/ncrna12020013","url":null,"abstract":"<p><p>Neuropathic pain represents a complex, prolonged pain state arising from lesions within the somatosensory nervous system. Despite significant advances in elucidating its pathophysiology, current therapeutic approaches remain largely symptomatic and frequently inadequate. MicroRNAs, a class of small non-coding RNAs that regulate gene expression post-transcriptionally, have recently emerged as critical modulators of neuronal excitability, neuroinflammation, and synaptic plasticity, which are crucial processes in the development and maintenance of neuropathic pain. This review summarizes the current evidence linking specific miRNAs to the onset and maintenance of neuropathic pain, with an emphasis on their roles in peripheral and central sensitization. The potential of miRNA-based biomarkers for diagnosis and prognostic evaluation is also highlighted. A thorough understanding of the complex miRNA regulatory networks underlying neuropathic pain could facilitate the development of novel, mechanism-based therapies and ultimately improve clinical outcomes.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"12 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paraspeckles Are Associated with the Activation and Nuclear Localization of Unphosphorylated miR-34a.","authors":"Graham H Read, Kristen McGreevy, Hanny Issawi, Tiffany Yang, Cynthia Tsang, Ihsan A Turk, Emily Rietdorf, Whitaker Cohn, David W Salzman, Julian P Whitelegge, Joanne B Weidhaas","doi":"10.3390/ncrna12020012","DOIUrl":"10.3390/ncrna12020012","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Canonical microRNAs possess a 5' phosphate required for Argonaute binding and activity. However, prior work identified an unphosphorylated, inactive nuclear pool of the important radiation-responsive microRNA, miR-34, that is rapidly phosphorylated and activated in response to ionizing radiation (IR). Here, we extend this work and investigate the role of paraspeckles, a phase-separated nuclear sub-compartment, and their association with the localization of unphosphorylated miR-34a. <b>Methods:</b> Mass spectrometry was performed to identify interacting partners of unphosphorylated mir-34. CRISPR-mediated deletion of the paraspeckle NEAT1_2 triple helix motif was performed to create an A549 cell line lacking paraspeckles (dTH). Activity and expression of mir-34a post-irradiation were evaluated by qRT-PCR and luciferase assays comparing dTH and wild-type (WT) A549 cell lines. In situ hybridization (ISH) was performed to evaluate mir-34a localization before and after IR, comparing dTH and WT cell lines. <b>Results:</b> Mass spectrometry identified paraspeckle proteins as significantly enriched interacting partners of unphosphorylated mir-34 mimics. By qRT-PCR and luciferase assays, we found that paraspeckle loss prevented radiation-induced early activation of unphosphorylated mir-34a. We found no difference in radiation-induced transcription of pri-miR-34a, but early processing to pre-miR-34a appeared delayed. ISH confirmed that loss of paraspeckles altered the nuclear localization of miR-34a before and after IR. <b>Conclusions:</b> These data suggest that paraspeckles are associated with nuclear localization and early radiation-responsive activation of unphosphorylated miR-34a. This suggests a coordinated nuclear sequestration of this important miR in its unphosphorylated state to enable an enhanced radiation response.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"12 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circular and Long Non-Coding RNAs in Cancer Metabolism: Dual Perspective of Biomarkers and Therapeutic Targets.","authors":"Francesca Pia Carbone, Stefania Hanau, Nicoletta Bianchi","doi":"10.3390/ncrna12020011","DOIUrl":"10.3390/ncrna12020011","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Metabolic reprogramming is a hallmark of cancer, enabling tumor cells to sustain proliferation, survive under metabolic stress, and develop therapeutic resistance. While oncogenic signaling pathways regulating cancer metabolism have been extensively studied, increasing evidence indicates that non-coding RNAs (ncRNAs) play essential roles in coordinating metabolic adaptation. This review aims to synthesize current knowledge on long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) as important but relatively less characterized regulators of cancer metabolic adaptation and discuss their potential as biomarkers and therapeutic targets. <b>Methods</b>: We analyzed their roles across multiple types of cancer, prioritizing studies that integrate ncRNA profiling with metabolomics and mechanistic investigations, with particular attention to their diagnostic, prognostic, and predictive value. <b>Results</b>: LncRNAs and circRNAs regulate major metabolic pathways, including glycolysis, mitochondrial function, glutaminolysis, lipid metabolism, and redox balance. They act through transcriptional and epigenetic mechanisms, protein scaffolding, peptide encoding, and miRNA sponging, frequently converging on key regulators such as HIF-1α, c-Myc, p53, AMPK, and mTOR. However, many reported associations remain largely correlative, with limited integration of quantitative metabolic flux analyses and insufficient validation in physiologically relevant models. <b>Conclusions</b>: Although lncRNAs and circRNAs constitute an important context-dependent regulatory layer linking oncogenic signaling to metabolic reprogramming, future studies should combine ncRNA perturbation with stable isotope tracing, fluxomics, spatial metabolomics, long-read sequencing, and single-cell approaches to define causal and spatially resolved metabolic functions. Such integrative strategies may improve biomarker development and support ncRNA-informed, metabolism-oriented therapeutic interventions.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"12 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13010655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vape-Associated lncRNA Transcript 1 (VALT1) Amplifies the Tumorigenic Effects of e-Cigarette Vapor in Lung Epithelial Cells.","authors":"Daniel Angelo R Mirador, Jose Lorenzo M Ferrer, Kim Denyse Hao Lin, Reynaldo L Garcia","doi":"10.3390/ncrna12020010","DOIUrl":"10.3390/ncrna12020010","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Lung cancer remains a major global health burden, largely driven by cigarette use. Although electronic cigarettes (e-cigarettes) are viewed as safer alternatives due to their reduced chemical load, growing evidence shows their vapor can disrupt cellular transcriptomes, including long noncoding RNAs (lncRNAs). In this study, we examined the regulation and function of vape-associated lncRNA transcript 1 (VALT1), a novel transcript upregulated in the oral transcriptomes of e-cigarette users and similarly elevated in non-small-cell lung cancer (NSCLC) tumors. <b>Methods</b>: Publicly available RNA-seq datasets were analyzed, and VALT1 was identified as an e-cigarette-responsive lncRNA. Its dose-dependent induction by e-cigarette smoke extract (eCSE) and cytoplasmic localization were confirmed via RT-qPCR. Its effects on cancer-associated phenotypes including proliferation, ROS detoxification, resistance to apoptosis, migration, cytoskeletal disorganization, and nuclear remodeling were assessed through overexpression and siRNA-mediated knockdown in A549 and BEAS-2B cells. <b>Results</b>: Acute eCSE exposure induced a biphasic, dose-dependent increase in VALT1 expression, accompanied by enhanced proliferation, ROS detoxification, apoptosis resistance, migration, cytoskeletal disorganization, and nuclear remodeling in A549 cells. VALT1 overexpression reproduced these phenotypes in both cell lines without eCSE treatment, whereas knockdown attenuated them. VALT1 promoted survival under cytotoxic stress in A549 but not BEAS-2B cells. <b>Conclusions</b>: These findings support an active role for VALT1 as an e-cigarette vapor-upregulated transcript that contributes to its phenotypic readout and enhances cellular survival under extracellular chemical stress-thereby aggravating tumorigenic phenotypes even in the absence of mutations that contribute to malignant transformation.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"12 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13010690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive <i>Schistosoma mansoni</i> Hierarchical Transcriptome Assembly Points to Novel lncRNAs Associated with Sexual Dimorphism.","authors":"Caio Felipe Freire, Thalles Souza-Lopes, Murilo Sena Amaral, Ana Carolina Tahira, Sergio Verjovski-Almeida","doi":"10.3390/ncrna12020009","DOIUrl":"10.3390/ncrna12020009","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Schistosomiasis is a neglected tropical disease affecting >200 million people worldwide. Praziquantel is the sole recommended drug against <i>Schistosoma mansoni</i>; however, it lacks activity against juvenile forms and cannot prevent reinfection. Thus, there is an urgent need to identify novel therapeutic targets. Long noncoding RNAs (lncRNAs) are known to regulate various biological processes in <i>S. mansoni</i>, including parasite pairing and fertility; therefore, screening for novel lncRNAs could reveal new potential targets. <b>Methods:</b> We compiled all publicly available RNA-seq data from the Sequence Read Archive (SRA) and performed a hierarchical transcriptome assembly using the multi-sample assembler Ryūtō, combined with version 10 of the <i>S. mansoni</i> genome. We applied HOMER for peak-calling and identification of histone marks and used weighted gene co-expression network analysis (WGCNA) to infer putative functions of lncRNAs in sexual dimorphism. <b>Results:</b> Using a robust pipeline, we identified 10,170 novel lncRNA genes comprising 16,990 novel lncRNA transcripts, including 8783 intergenic, 7918 antisense, and 289 intronic lncRNA transcripts. Most (78.7%) have histone regulatory marks (H3K4me3, H3K27me3, H3K27ac, or H4K20me1) near their transcription start sites, indicating potential expression regulation. Comparing male and female samples, we identified 1991 differentially expressed genes (FDR < 5%, |log₂FC| ≥ 1.5), including 296 known lncRNAs and 339 novel lncRNAs. WGCNA identified hub lncRNAs within co-expression modules, and Gene Ontology enrichment analyses (FDR ≤ 5%) suggest that these lncRNAs are involved in cell differentiation and morphogenesis pathways. <b>Conclusions:</b> We provide a comprehensive catalog of <i>S. mansoni</i> lncRNAs. These findings offer opportunities to discover potential new therapeutic targets, advancing the future development of anti-schistosome therapies.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"12 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13010763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short and Long Non-Coding RNAs in Renal Cell Carcinoma.","authors":"Monia Cecati, Valentina Pozzi, Valentina Schiavoni, Giuseppina Barrasso, Veronica Pompei, Daniela Marzioni, Nicoletta Bonci, Stefania Fumarola, Andrea Ballini, Davide Sartini, Roberto Campagna","doi":"10.3390/ncrna12020008","DOIUrl":"10.3390/ncrna12020008","url":null,"abstract":"<p><p>Renal cell carcinoma (RCC) represents the most frequent kidney malignancy and remains a major clinical challenge due to its often silent onset, high metastatic potential, and limited responsiveness to conventional chemotherapy. Increasing evidence indicates that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are key regulators of RCC tumorigenesis, progression, and therapy resistance. Rather than providing a purely descriptive overview, this review focuses on emerging mechanistic paradigms through which ncRNAs actively shape tumor behavior and therapeutic response in RCC. This review summarizes current knowledge on the biological and clinical relevance of ncRNAs in RCC, highlighting their dual roles as oncogenic drivers or tumor suppressors through the modulation of pathways involved in proliferation, apoptosis, angiogenesis, invasion, immune evasion, metabolic reprogramming, and ferroptosis. Particular emphasis is placed on mechanistically defined ncRNA regulatory axes controlling ferroptosis, autophagy, metabolic reprogramming, and immune escape, as well as on ncRNA-mediated intercellular communication via extracellular vesicles, which promotes the dissemination of resistance to targeted therapies. The review also addresses ncRNA-based diagnostic and prognostic applications, including miRNA signatures capable of discriminating RCC subtypes and circulating ncRNAs as minimally invasive biomarkers. Moreover, the manuscript discusses ncRNA-mediated mechanisms of resistance to targeted therapies such as sunitinib, sorafenib, and axitinib, emphasizing regulatory networks involving miRNA targets, lncRNA-miRNA sponging, RNA-binding proteins, extracellular vesicle transfer, and epigenetic modulation. Emerging therapeutic opportunities are also addressed, including strategies aimed at inhibiting oncogenic ncRNAs or restoring tumor-suppressive ncRNAs to enhance drug sensitivity and improve patient stratification.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"12 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13010606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}