Non-Coding RNAPub Date : 2025-07-30DOI: 10.3390/ncrna11040058
Leandro Teodoro Júnior, Mari Cleide Sogayar
{"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}
Non-Coding RNAPub Date : 2025-07-29DOI: 10.3390/ncrna11040056
Raffaele Frazzi, Enrico Farnetti, Davide Nicoli
{"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}
Non-Coding RNAPub Date : 2025-07-28DOI: 10.3390/ncrna11040055
Irma A Jiménez-Ramírez, Miguel A Uc-Chuc, Luis Carlos Rodríguez Zapata, Enrique Castaño
{"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}
Non-Coding RNAPub Date : 2025-07-18DOI: 10.3390/ncrna11040054
Lola Jaque-Cabrera, Julia Buggiani, Jérôme Bignon, Patricia Daira, Nathalie Bernoud-Hubac, Jean-René Martin
{"title":"Knockdown of the snoRNA-Jouvence Blocks the Proliferation and Leads to the Death of Human Primary Glioblastoma Cells.","authors":"Lola Jaque-Cabrera, Julia Buggiani, Jérôme Bignon, Patricia Daira, Nathalie Bernoud-Hubac, Jean-René Martin","doi":"10.3390/ncrna11040054","DOIUrl":"10.3390/ncrna11040054","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Cancer research aims to understand the cellular and molecular mechanisms involved, in order to identify new therapeutic targets and provide patients with more effective therapies that generate fewer side undesirable and toxic effects. Previous studies have demonstrated the role of small nucleolar RNAs (snoRNAs) in many physiological and pathological cellular processes, including cancers. SnoRNAs are a group of non-coding RNAs involved in different post-transcriptional modifications of ribosomal RNAs. Recently, we identified a new snoRNA (jouvence), first in Drosophila, and thereafter, by homology, in humans. <b>Methods</b>: Here, we characterize the effect of the knockdown of jouvence by a sh-lentivirus on human primary patient-derived glioblastoma cells. <b>Results</b>: The sh-lentivirus anti-jouvence induces a significant decrease in cell proliferation and leads to cell death. EdU staining confirmed this decrease, while TUNEL also showed the presence of apoptotic cells. An RNA-Seq analysis revealed a decrease, in particular, in the level of BAALC, a gene known to potentiate the oncogenic ERK pathway and deregulating p21, leading to cell cycle blockage. <b>Conclusions</b>: Altogether, these results allow the hypothesis that the knockdown of jouvence could potentially be used as a new anti-cancer treatment (sno-Therapy), especially against glioblastoma and also, potentially, against acute myeloid leukemia (AML) due to the BAALC deregulation.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699124","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}
Non-Coding RNAPub Date : 2025-07-18DOI: 10.3390/ncrna11040053
Raffaele Garraffo, Manuel Beltran Nebot
{"title":"Direct circRNA-mRNA Binding Controls mRNA Fate: A New Mechanism for circRNAs.","authors":"Raffaele Garraffo, Manuel Beltran Nebot","doi":"10.3390/ncrna11040053","DOIUrl":"10.3390/ncrna11040053","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) are covalently closed RNA molecules generated through a non-canonical splicing event known as back-splicing. This particular class of non-coding RNAs has attracted growing interest due to its evolutionary conservation across eukaryotes, high expression in the central nervous system, and frequent dysregulation in various pathological conditions, including cancer. Traditionally, circRNAs have been characterised by their ability to function as microRNA (miRNA) and protein sponges. However, recent discoveries from multiple research groups have uncovered a novel and potentially transformative mechanism of action: the direct interaction of circRNAs with messenger RNAs (mRNAs) to regulate their fate. These interactions can influence mRNA stability and translation, revealing a new layer of post-transcriptional gene regulation. In this review, we present and analyse the latest evidence supporting the emerging role of circRNAs in diverse biological contexts. We highlight the growing body of research demonstrating circRNA-mRNA interactions as a functional regulatory mechanism and explore their involvement in key physiological and pathophysiological processes. Understanding this novel mechanism expands our knowledge of RNA-based regulation and opens new opportunities for therapeutic strategies targeting circRNA-mRNA networks in human disease.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699123","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}
Non-Coding RNAPub Date : 2025-07-04DOI: 10.3390/ncrna11040052
Beshoy Armanios, Jing Jin, Holly Kolmel, Ankit P Laddha, Neha Mishra, Jose E Manautou, Xiao-Bo Zhong
{"title":"Unraveling the Regulatory Impact of LncRNA Hnf1aos1 on Hepatic Homeostasis in Mice.","authors":"Beshoy Armanios, Jing Jin, Holly Kolmel, Ankit P Laddha, Neha Mishra, Jose E Manautou, Xiao-Bo Zhong","doi":"10.3390/ncrna11040052","DOIUrl":"10.3390/ncrna11040052","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Long non-coding RNAs (lncRNAs) play significant roles in tissue development and disease progression and have emerged as crucial regulators of gene expression. The hepatocyte nuclear factor alpha antisense RNA 1 (HNF1A-AS1) lncRNA is a particularly intriguing regulatory molecule in liver biology that is involved in the regulation of cytochrome P450 enzymes via epigenetic mechanisms. Despite the growing recognition of lncRNAs in liver disease, the comprehensive role of HNF1A-AS1 in liver function remains unclear. This study aimed to investigate the roles of the mouse homolog of the human HNF1A-AS1 lncRNA HNF1A opposite strand 1 (Hnf1aos1) in liver function, gene expression, and cellular processes using a mouse model to identify potential therapeutic targets for liver disorders. <b>Methods:</b> The knockdown of Hnf1aos1 was performed in in vitro mouse liver cell lines using siRNA and in vivo livers of AAV-shRNA complexes. Changes in the global expression landscapes of mRNA and proteins were revealed using RNA-seq and proteomics, respectively. Changes in the selected genes were further validated via real-time quantitative polymerase chain reaction (RT-qPCR). Phenotypic changes were assessed via histological and absorbance-based assays. <b>Results:</b> After the knockdown of Hnf1aos1, RNA-seq and proteomics analysis revealed the differential gene expression of the mRNAs and proteins involved in the processes of molecular transport, liver regeneration, and immune signaling pathways. The downregulation of ABCA1 and SREBF1 indicates their role in cholesterol transport and fatty acid and triglyceride synthesis. Additionally, significant reductions in hepatic triglyceride levels were observed in the Hnf1aos1-knockdown group, underscoring the impact on lipid regulation. Notably, the knockdown of Hnf1aos1 also led to an almost complete depletion of CYP7A1, the rate-limiting enzyme in bile acid synthesis, highlighting its role in cholesterol homeostasis and hepatotoxicity. Histological assessments confirmed these molecular findings, with increased hepatic inflammation, hepatocyte swelling, and disrupted liver architecture observed in the Hnf1aos1-knockdown mice. <b>Conclusions:</b> This study illustrated that Hnf1aos1 is a critical regulator of liver health, influencing both lipid metabolism and immune pathways. It maintains hepatic lipid homeostasis, modulates lipid-induced inflammatory responses, and contributes to viral immunity, indirectly affecting glucose and lipid metabolic balance.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699127","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}
Non-Coding RNAPub Date : 2025-07-03DOI: 10.3390/ncrna11040051
Mario García-Domínguez
{"title":"Role of ncRNAs in the Development of Chronic Pain.","authors":"Mario García-Domínguez","doi":"10.3390/ncrna11040051","DOIUrl":"10.3390/ncrna11040051","url":null,"abstract":"<p><p>Chronic pain is a multifactorial and complex condition that significantly affects individuals' quality of life. The underlying mechanisms of chronic pain involve complex alterations in neural circuits, gene expression, and cellular signaling pathways. Recently, ncRNAs, such as miRNAs, lncRNAs, circRNAs, and siRNAs, have been identified as crucial regulators in the pathophysiology of chronic pain. These ncRNAs modulate gene expression at both the transcriptional and post-transcriptional levels, affecting pain-related pathways like inflammation, neuronal plasticity, and sensory processing. miRNAs have been shown to control genes involved in pain perception and nociceptive signaling, while lncRNAs interact with chromatin remodeling factors and transcription factors to modify pain-related gene expression. CircRNAs act as sponges for miRNAs, thereby influencing pain mechanisms. siRNAs, recognized for their gene-silencing capabilities, also participate in regulating the expression of pain-related genes. This review examines the diverse roles of ncRNAs in chronic pain, emphasizing their potential as biomarkers for pain assessment and as targets for novel therapeutic strategies. A profound understanding of the ncRNA-mediated regulatory networks involved in chronic pain could result in more effective and personalized pain management solutions.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699126","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}
Non-Coding RNAPub Date : 2025-06-25DOI: 10.3390/ncrna11040049
Weijun Yi, Jason R Miller, Gangqing Hu, Donald A Adjeroh
{"title":"LncRNA Subcellular Localization Across Diverse Cell Lines: An Exploration Using Deep Learning with Inexact <i>q</i>-mers.","authors":"Weijun Yi, Jason R Miller, Gangqing Hu, Donald A Adjeroh","doi":"10.3390/ncrna11040049","DOIUrl":"10.3390/ncrna11040049","url":null,"abstract":"<p><p><b>Background:</b> Long non-coding Ribonucleic Acids (lncRNAs) can be localized to different cellular compartments, such as the nuclear and the cytoplasmic regions. Their biological functions are influenced by the region of the cell where they are located. Compared to the vast number of lncRNAs, only a relatively small proportion have annotations regarding their subcellular localization. It would be helpful if those few annotated lncRNAs could be leveraged to develop predictive models for localization of other lncRNAs. <b>Methods:</b> Conventional computational methods use <i>q</i>-mer profiles from lncRNA sequences and train machine learning models such as support vector machines and logistic regression with the profiles. These methods focus on the exact <i>q</i>-mer. Given possible sequence mutations and other uncertainties in genomic sequences and their role in biological function, a consideration of these variabilities might improve our ability to model lncRNAs and their localization. Thus, we build on inexact <i>q</i>-mers and use machine learning/deep learning techniques to study three specific problems in lncRNA subcellular localization, namely, prediction of lncRNA localization using inexact <i>q</i>-mers, the issue of whether lncRNA localization is cell-type-specific, and the notion of switching (lncRNA) genes. <b>Results:</b> We performed our analysis using data on lncRNA localization across 15 cell lines. Our results showed that using inexact <i>q</i>-mers (with <i>q</i> = 6) can improve the lncRNA localization prediction performance compared to using exact <i>q</i>-mers. Further, we showed that lncRNA localization, in general, is not cell-line-specific. We also identified a category of LncRNAs which switch cellular compartments between different cell lines (we call them switching lncRNAs). These switching lncRNAs complicate the problem of predicting lncRNA localization using machine learning models, showing that lncRNA localization is still a major challenge.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699125","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: Piergentili et al. miR-125 in Breast Cancer Etiopathogenesis: An Emerging Role as a Biomarker in Differential Diagnosis, Regenerative Medicine, and the Challenges of Personalized Medicine. <i>Non-Coding RNA</i> 2024, <i>10</i>, 16.","authors":"Roberto Piergentili, Enrico Marinelli, Gaspare Cucinella, Alessandra Lopez, Gabriele Napoletano, Giuseppe Gullo, Simona Zaami","doi":"10.3390/ncrna11040050","DOIUrl":"10.3390/ncrna11040050","url":null,"abstract":"<p><p>There was an error in the original publication [...].</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626791","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}