Non-Coding RNA最新文献

{"title":"Navigating the Landscape of Exosomal microRNAs: Charting Their Pivotal Role as Biomarkers in Hematological Malignancies.","authors":"Manlio Fazio, Fabio Stagno, Giuseppa Penna, Giuseppe Mirabile, Alessandro Allegra","doi":"10.3390/ncrna11050064","DOIUrl":"10.3390/ncrna11050064","url":null,"abstract":"<p><p>Under physiological and pathological conditions, all cells release extracellular vesicles named exosomes, which act as transporters of lipidic, protein, and genetic material from parent to recipient cells. Neoplastic cells can secrete higher number of exosomes to exert pro-tumoral effects such as microenvironmental changes, disease progression, immunosuppression and drug-resistance. This holds true for both organ-specific cancers and hematologic malignancies. One of the most important components of exosomal cargo are microRNAs which can mediate all the abovementioned effects. More specifically, microRNAs are small non-coding RNAs, routinely detected through quantitative real-time PCR, which act as translational suppressors by regulating protein-coding genes. Considering their high stability in all body fluids and viability in circulation, research is currently focusing on this type of RNAs for the so called \"liquid biopsy\", a non-invasive tool for disease diagnosis and longitudinal monitoring. However, several issues remain to be solved including the lack of standardized protocols for exosome isolation and miRNA detection. Starting with this premise, our review aims to provide a wide description of the known microRNA panels employed in the prominent hematological malignancies, which will hopefully redefine the approach to these very challenging diseases in the near future.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 5","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113965","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":"Same Fragments, Different Diseases: Analysis of Identical tRNA Fragments Across Diseases Utilizing Functional and Abundance-Based Databases.","authors":"Adesupo Adetowubo, Sathyanarayanan Vaidhyanathan, Andrey Grigoriev","doi":"10.3390/ncrna11050063","DOIUrl":"10.3390/ncrna11050063","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Transfer RNA-derived fragments (tRFs) are small non-coding RNAs increasingly implicated in gene regulation and disease, yet their target specificity and disease relevance remain poorly understood. This is an exploratory study that investigates the phenomenon of identical tRF sequences reported in distinct disease contexts and evaluates the consistency between experimental findings and predictions from both target-based and abundance-based tRF databases. <b>Methods:</b> Five tRFs with identical sequences across at least two peer-reviewed disease studies were selected from a recent systematic review. Their validated targets and disease associations were extracted from the literature. Motifs and predicted targets were cross-referenced using three target-oriented databases: tatDB, tRFTar, and tsRFun. In parallel, the abundance enrichment of cancer-associated tRFs was assessed in OncotRF and MINTbase using TCGA-based abundance data. <b>Results:</b> Among the five tRFs, only LeuAAG-001-N-3p-68-85 showed complete alignment between experimental data and both tatDB and tRFTar predictions. Most of the other four displayed at least partial overlaps in motif/binding regions with some of validated targets. tRF abundance data from MINTbase and OncotRF showed inconsistent enrichment, with only AlaAGC-002-N-3p-58-75 exhibiting concordance with its experimentally validated cancer type. Most functionally relevant tRFs were not strongly represented in abundance-only databases. <b>Conclusions:</b> Given the limited number of tRFs analyzed, this study serves primarily as a pilot analysis designed to generate hypotheses and guide future in-depth research, rather than offering comprehensive conclusions. We did, however, illustrate how the analysis of tRFs can benefit from utilizing currently available databases. Target-based databases more closely reflected experimental evidence for mechanistic details when a tRF or a motif match is found. Yet all database types are incomplete, including the abundance-focused tools, which often fail to capture disease-specific regulatory roles of tRFs. These findings underscore the importance of using integrated data sources for tRF annotation. As a pilot analysis, the study provides insights into how identical tRF sequences might function differently across disease contexts, highlighting areas for further investigation while pointing out the limitations of relying on expression data alone to infer functional relevance.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 5","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113970","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":"Partners in Silencing: Decoding the Mammalian Argonaute Interactome.","authors":"Srinaath Narasimhan, Stefan J Erkeland","doi":"10.3390/ncrna11040062","DOIUrl":"10.3390/ncrna11040062","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are key post-transcriptional regulators controlling gene expression across several cellular processes, including development, proliferation, and apoptosis. Their biogenesis involves a multi-step pathway, including the processing of primary transcripts and the assembly of the RNA-Induced Silencing Complex (RISC) with Argonaute (AGO) proteins at its core. This review provides a comprehensive overview of the molecular dynamics of miRNA-loaded RISC (miRISC), focusing on the post-translational modifications, the interactors of AGOs and the mechanisms that fine-tune and coordinate miRISC activity. The composition of miRISC influences AGO stability, localization, and silencing efficiency, thereby maintaining cellular homeostasis and development and mediating the response to various types of cellular stress. Uncommon regulatory mechanisms, including AGO modifications during, e.g., hypoxia or Type 2 T cell responses and miRISC functionality, with myriad RNA-binding proteins (RBPs), will be discussed. This review aims at highlighting the recent advances in the understanding of the intricate regulation of miRISC-driven gene silencing.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12388510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963131","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":"The Role of Non-Coding RNAs in the Regulation of Oncogenic Pathways in Breast and Gynaecological Cancers.","authors":"Ammar Ansari, Aleksandra Szczesnowska, Natalia Haddad, Ahmed Elbediwy, Nadine Wehida","doi":"10.3390/ncrna11040061","DOIUrl":"10.3390/ncrna11040061","url":null,"abstract":"<p><p>Female cancers such as breast and gynaecological cancers contribute to a significant global health burden and are a leading cause of fatality among women. With current treatment options often limited by resistance to cytotoxic drugs, side effects and lack of specificity to the cancer, there is a pressing need for alternative treatments. Recent research has highlighted the promising role of non-coding RNAs (ncRNA) in regulating these issues and providing more targeted approaches to suppressing key cancer pathways. This review explores the involvement of the various types of non-coding RNAs in regulating key oncogenic pathways, namely, the MAPK, PI3K/Akt/mTOR, Wnt/β-catenin and p53 pathways, in a range of female cancers such as breast, cervical, ovarian and endometrial cancers. Evidence from a multitude of studies suggests that non-coding RNAs function as double-edged swords, serving as both oncogenes and tumour suppressors, depending on their expression and cellular interactions. By mapping and investigating these regulatory interactions, this review demonstrates the complexity and dual functionality of ncRNAs in cancer. Understanding these complex mechanisms is essential for the development of new and effective ncRNA-based diagnostic methods and targeted therapies in female cancer treatment.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12388849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963138","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":"MALAT1 Expression Is Deregulated in miR-34a Knockout Cell Lines.","authors":"Andrea Corsi, Tonia De Simone, Angela Valentino, Elisa Orlandi, Chiara Stefani, Cristina Patuzzo, Stefania Fochi, Maria Giusy Bruno, Elisabetta Trabetti, John Charles Rotondo, Chiara Mazziotta, Maria Teresa Valenti, Alessandra Ruggiero, Donato Zipeto, Cristina Bombieri, Maria Grazia Romanelli","doi":"10.3390/ncrna11040060","DOIUrl":"10.3390/ncrna11040060","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Non-coding microRNA-34a (miR-34a) regulates the expression of key factors involved in several cellular processes, such as differentiation, apoptosis, proliferation, cell cycle, and senescence. Deregulation of the expression of these factors is implicated in the onset and progression of several human diseases, including cancer, neurodegenerative disorders, and pathologies associated with viral infections and inflammation. Despite numerous studies, the molecular mechanisms regulated by miR-34a remain to be fully understood. The present study aimed to generate miR-34a knockout cell lines to identify novel genes potentially regulated by its expression. <b>Methods:</b> We employed the CRISPR-Cas9 gene editing system to knock out the hsa-miR-34a gene in HeLa and 293T cell lines, two widely used models for studying molecular and cellular mechanisms. We compared proliferation rates and gene expression profiles via RNA-seq and qPCR analyses between the wild-type and miR-34a KO cell lines. <b>Results:</b> Knockout of miR-34a resulted in a decreased proliferation rate in both cell lines. Noteworthy, the ablation of miR-34a resulted in increased expression of the long non-coding RNA MALAT1. Additionally, miR-34a-5p silencing in the A375 melanoma cell line led to MALAT1 overexpression. <b>Conclusions:</b> Our findings support the role of the miR-34a/MALAT1 axis in regulating proliferation processes.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12388995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963093","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":"DEAD-Box Helicase 3 Modulates the Non-Coding RNA Pool in Ribonucleoprotein Condensates During Stress Granule Formation.","authors":"Elizaveta Korunova, B Celia Cui, Hao Ji, Aliaksandra Sikirzhytskaya, Srestha Samaddar, Mengqian Chen, Vitali Sikirzhytski, Michael Shtutman","doi":"10.3390/ncrna11040059","DOIUrl":"10.3390/ncrna11040059","url":null,"abstract":"<p><p>Stress granule formation is a type of liquid-liquid phase separation in the cytoplasm, leading to RNA-protein condensates that are associated with various cellular stress responses and implicated in numerous pathologies, including cancer, neurodegeneration, inflammation, and cellular senescence. One of the key components of mammalian stress granules is the DEAD-box RNA helicase DDX3, which unwinds RNA in an ATP-dependent manner. DDX3 is involved in multiple steps of RNA metabolism, facilitating gene transcription, splicing, and nuclear export and regulating cytoplasmic translation. In this study, we investigate the role of the RNA helicase DDX3's enzymatic activity in shaping the RNA content of ribonucleoprotein (RNP) condensates formed during arsenite-induced stress by inhibiting DDX3 activity with RK-33, a small molecule previously shown to be effective in cancer clinical studies. Using the human osteosarcoma U2OS cell line, we purified the RNP granule fraction and performed RNA sequencing to assess changes in the RNA pool. Our results reveal that RK-33 treatment alters the composition of non-coding RNAs within the RNP granule fraction. We observed a DDX3-dependent increase in circular RNA (circRNA) content and alterations in the granule-associated intronic RNAs, suggesting a novel role for DDX3 in regulating the cytoplasmic redistribution of non-coding RNAs.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12388690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963066","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":"The Good, the Bad, or Both? Unveiling the Molecular Functions of LINC01133 in Tumors.","authors":"Leandro Teodoro Júnior, Mari Cleide Sogayar","doi":"10.3390/ncrna11040058","DOIUrl":"10.3390/ncrna11040058","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Increasing evidence suggests that lncRNAs are core regulators in the field of tumor progression, with context-specific functions in oncogenic tumorigenesis. LINC01133, a lncRNA that has been identified as both an oncogene and a tumor suppressor, remains largely unexplored in terms of its molecular mechanisms. The purpose of this study was to conduct an in silico analysis, incorporating literature research on various cancer types, to investigate the structural and functional duality of LINC01133. This analysis aimed to identify pathways influenced by LINC01133 and evaluate its mechanism of action as a potential therapeutic target and diagnostic biomarker. <b>Methods:</b> In silico analyses and a narrative review of the literature were performed to predict conserved structural elements, functional internal loops, and overall conservation of the LINC01133 sequence among different vertebrate organisms, summarizing the empirical evidence regarding its roles as a tumor suppressor and tumor-promoting roles in various types of tumors. <b>Results:</b> LINC01133 harbors the evolutionarily conserved structural regions that might allow for binding to relevant driver signaling pathways, substantiating its specific functionality. Its action extends beyond classical tumor mechanisms, affecting proliferation, migration, invasion, and epigenetic pathways in various types of tumors, as indicated by the in silico results and narrative review of the literature we present here. Clinical outcome associations pointed to its potential as a biomarker. <b>Conclusions:</b> The dual character of LINC01133 in tumor biology further demonstrates its prospective therapeutic value, but complete elucidation of its mechanisms of action requires further investigation. This study establishes LINC01133 as a multifaceted lncRNA, supporting context-specific strategies in targeting its pathways, and calls for expanded research to harness its full potential in oncology.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12389352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963059","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":"Correction: Garmaa et al. A Systematic Review and Meta-Analysis of microRNA Profiling Studies in Chronic Kidney Diseases. <i>Non-Coding RNA</i> 2024, <i>10</i>, 30.","authors":"Gantsetseg Garmaa, Stefania Bunduc, Tamás Kói, Péter Hegyi, Dezső Csupor, Dariimaa Ganbat, Fanni Dembrovszky, Fanni Adél Meznerics, Ailar Nasirzadeh, Cristina Barbagallo, Gábor Kökény","doi":"10.3390/ncrna11040057","DOIUrl":"10.3390/ncrna11040057","url":null,"abstract":"<p><p><b>Text Correction</b> [...].</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12388611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963117","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":"circRNA/miRNA Networks Regulate KLF4 in Tumor Development.","authors":"Raffaele Frazzi, Enrico Farnetti, Davide Nicoli","doi":"10.3390/ncrna11040056","DOIUrl":"10.3390/ncrna11040056","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Krüppel-like factor 4 (<i>KLF4</i>) emerged as an epigenetically regulated gene in a variety of settings, including cell reprogramming and malignant cell proliferation. The aim of the present manuscript is to explore the relationship described in recent years between circular RNAs, miRNAs, and <i>KLF4</i>. These have been shown to be involved in cancers having diverse histological origins, including some of the most prevalent and deadly tumors for the human population. Expression and protein levels of this transcription factor correlate with invasiveness and prognosis in a context- and tissue-specific fashion. <b>Methods</b>: The literature was obtained through two main PubMed queries. The first is \"miRNA and KLF4 and cancer\" and is limited to the last 5 years. The second is \"circRNA and KLF4\", which yielded publications between 2013 and 2024. The oncological publications were selected. <b>Results</b>: A number of circRNA/miRNA axes that regulate the downstream transcription factor <i>KLF4</i> emerged in the last few years. circRNAs act as sponges for miRNAs and synergize with <i>KLF4</i>, which can function as either a tumor promoter or suppressor in different tumors. <b>Conclusions</b>: The axes represented by circRNA/miRNA/<i>KLF4</i> emerged as a new layer of epigenetic regulation. These RNA-based modulators explain the complex regulation of this transcription factor and open the way to new therapeutic targeting possibilities.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12388550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963058","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":"Small Nucleolar RNA from <i>S. cerevisiae</i> Binds to Phosphatidylinositol 4,5-Bisphosphate.","authors":"Irma A Jiménez-Ramírez, Miguel A Uc-Chuc, Luis Carlos Rodríguez Zapata, Enrique Castaño","doi":"10.3390/ncrna11040055","DOIUrl":"10.3390/ncrna11040055","url":null,"abstract":"<p><p><b>Background</b>: snoRNAs have traditionally been known for their role as guides in post-transcriptional rRNA modifications. Previously, our research group identified several RNAs that may bind to PIP2 with LIPRNA-seq. Among them, snR191 stood out due to its potential specific interaction with this lipid, distinguishing itself from other snoRNAs. However, a detailed study is needed to define the molecular interactions between RNA and lipids, which remain unknown but may serve as a mechanism for transport or liquid-liquid phase separation. This study aimed to determine the interaction between a snoRNA called snR191 and PIP2. <b>Method</b>: A novel methodology for RNA-PIP2 interaction was carried out. Total RNA from <i>Saccharomyces cerevisiae</i> was incubated with PIP2-bound nitrocellulose membranes and RT-PCR reactions. We performed the prediction of snR191-PIP2 interaction by molecular docking and in silico mutations of snoR191. <b>Results</b>: From LIPRNA-seq analysis, we identified that PIP2-bound RNAs were significantly enriched in diverse biological processes, including transmembrane transport and redox functions. Our RNA-PIP2 interaction approach was successful. We demonstrated that snR191 specifically interacts with PIP2 in vitro. The elimination of DNA ensured that the interaction assay was RNA-specific, strengthening the robustness of the experiment. PIP2 was docked to snR191 in a stem-loop-stem motif. Six hydrogen bonds across four nucleotides mediated the PIP2-snR191 interaction. Finally, mutations in snR191 affected the structural folding. <b>Conclusions</b>: In this study, we demonstrate the effectiveness of a new methodology for determining RNA-lipid interactions, providing strong evidence for the specific interaction between snR191 and PIP2. Integrating biochemical and computational approaches has allowed us to understand the binding of these biomolecules. Therefore, this work significantly broadens our understanding of snR191-PIP2 interactions and opens new perspectives for further research.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12389098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963049","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}