Non-Coding RNA最新文献

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The Chromosome 19 microRNA Cluster Facilitates Cancer Stemness in Hepatocellular Carcinoma. 19号染色体microRNA簇促进肝癌的癌变。
IF 3.6
Non-Coding RNA Pub Date : 2025-10-29 DOI: 10.3390/ncrna11060074
Marian T Underwood, Varsha Devarapalli, Goodwin G Jinesh, John H Lockhart, Marco Napoli, Nino Mtchedlidze, Elsa R Flores, Andrew S Brohl
{"title":"The Chromosome 19 microRNA Cluster Facilitates Cancer Stemness in Hepatocellular Carcinoma.","authors":"Marian T Underwood, Varsha Devarapalli, Goodwin G Jinesh, John H Lockhart, Marco Napoli, Nino Mtchedlidze, Elsa R Flores, Andrew S Brohl","doi":"10.3390/ncrna11060074","DOIUrl":"10.3390/ncrna11060074","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Hepatocellular carcinoma (HCC) is one of the world's deadliest cancers; however, the mechanisms that contribute to its aggressiveness are poorly understood. In the recent literature, overexpression of the Chromosome 19 MicroRNA Cluster (C19MC) has been associated with an aggressive phenotype and unfavorable prognosis in HCC. However, the molecular consequences of C19MC overexpression in HCC remain poorly understood. <b>Methods</b>: Here, we created a constitutive C19MC-overexpressing HCC model and used two different CRISPR-engineered C19MC-overexpressing HCC models to analyze phenotype and transcriptomic changes. <b>Results</b>: We observed that C19MC overexpression induces cancer stem cell (CSC) phenotypic features in vitro and analyzed transcriptomic changes in genes correlating with stemness, such as NFκB and EMT. <b>Conclusions</b>: C19MC induces changes in HCC that are consistent with stemness and aggression, which provides a better understanding of why C19MC could be a biomarker of poor prognosis.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12641929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145588295","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}
引用次数: 0
Exploring microRNAs, One Cell at a Time. 一次一个细胞地探索微小rna。
IF 3.6
Non-Coding RNA Pub Date : 2025-10-22 DOI: 10.3390/ncrna11060073
Jessica Kreutz, Tijana Mitić, Andrea Caporali
{"title":"Exploring microRNAs, One Cell at a Time.","authors":"Jessica Kreutz, Tijana Mitić, Andrea Caporali","doi":"10.3390/ncrna11060073","DOIUrl":"10.3390/ncrna11060073","url":null,"abstract":"<p><p>The emergence of single-cell sequencing and computational analysis has dramatically improved our understanding of cellular diversity and gene expression dynamics. The rapid advancement of high-throughput omics technologies has led to an exponential growth in biological data. However, many gene regulatory processes at the single-cell level remain underexplored, especially those regulated by post-transcriptional mechanisms involving microRNAs (miRNAs). miRNAs are essential regulators of gene expression, affecting cellular functions in both normal and disease states. Recent innovations, such as single-cell gene expression profiling and bioinformatic analysis, have enabled comprehensive studies that uncover previously hidden miRNA profiles. In this context, we present experimental tools and computational methods for analysing cell-specific miRNA abundance and investigating their mechanisms. These approaches are expected to reveal the complex nature of miRNA biology and, more broadly, enhance our understanding of life sciences and diseases.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12641660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145588361","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}
引用次数: 0
Identification and Functions of lncRNAs in Fungi. 真菌中lncrna的鉴定和功能。
IF 3.6
Non-Coding RNA Pub Date : 2025-10-07 DOI: 10.3390/ncrna11050072
Javier Avalos, Adrián Perera-Bonaño, M Carmen Limón
{"title":"Identification and Functions of lncRNAs in Fungi.","authors":"Javier Avalos, Adrián Perera-Bonaño, M Carmen Limón","doi":"10.3390/ncrna11050072","DOIUrl":"10.3390/ncrna11050072","url":null,"abstract":"<p><p>Long noncoding RNAs (lncRNAs) are transcripts generated by polymerase II, therefore subject to 5' capping and 3' polyadenylation, categorized as such when they are at least 200 nt in size and lack coding function. The lncRNAs were initially interpreted as spurious transcription products, but over the last two decades an increasing amount of evidence has accumulated for regulatory functions. They are found in all taxonomic groups, including bacteria, archaea, fungi, animals and plants. In fungi, global analyses anticipate their presence in higher numbers than initially expected considering the simplicity of these organisms. Except for the numerous studies performed in budding and fission yeast, relatively few lncRNAs have been investigated in sufficient detail in the rest of the fungi, but their number has increased steadily in recent years. The lncRNAs can be transcribed from intergenic regions or coincide totally or partially with protein-coding genes, in which case they are most frequently antisense transcripts. Their regulatory functions can be performed by a wide variety of mechanisms, both in <i>cis</i> on neighboring genes and in <i>trans</i> on distant genes or on proteins. Among the most frequent mechanisms are interference on the transcription of neighboring genes and generation of epigenetic modifications in the environment of target genes. Here, we review the most representative cases of global analyses of the presence of lncRNAs in fungal transcriptomes and describe the lncRNAs that have received more detailed attention.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 5","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12566771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145391683","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}
引用次数: 0
microRNA Biomarkers in Paediatric Infection Diagnostics-Bridging the Gap Between Evidence and Clinical Application: A Scoping Review. 儿科感染诊断中的microRNA生物标志物-弥合证据与临床应用之间的差距:范围综述。
IF 3.6
Non-Coding RNA Pub Date : 2025-09-24 DOI: 10.3390/ncrna11050071
Oenone Rodgers, Anna De Beer, Thomas Waterfield
{"title":"microRNA Biomarkers in Paediatric Infection Diagnostics-Bridging the Gap Between Evidence and Clinical Application: A Scoping Review.","authors":"Oenone Rodgers, Anna De Beer, Thomas Waterfield","doi":"10.3390/ncrna11050071","DOIUrl":"10.3390/ncrna11050071","url":null,"abstract":"<p><strong>Background: </strong>Distinguishing between bacterial and viral infections in children remains a significant challenge for clinicians. Traditional biomarkers have limited utility, often leading to antibiotic overprescription due to clinician uncertainty. With rising antimicrobial resistance, novel biomarkers are needed to improve diagnosis. This scoping review examines current host miRNA biomarkers for acute bacterial and viral infections in children (0-18), focusing on study methods, diagnostic metrics, and research gaps to support clinical translation.</p><p><strong>Results: </strong>Of the 1147 articles identified, 36 studies were included. Notably, 72.2% of the studies originated from Asia, and the distribution across the paediatric age groups was relatively even. A total of 17 miRNAs were validated in at least two independent studies. Three miRNAs, hsa-miR-182-5p, hsa-miR-363-3p, and hsa-miR-206, were consistently associated with bacterial infection in children. Meanwhile, nine miRNAs were associated with viral infections: hsa-miR-155, hsa-miR-29a-3p, hsa-miR-155-5p, hsa-miR-150-5p, hsa-miR-140-3p, hsa-miR-142-3p, hsa-miR-149-3p, hsa-miR-210-3p, and hsa-miR-34a-5p. Across the 12 studies reporting diagnostic accuracy metrics, miRNA biomarkers exhibited a sensitivity ranging from 70% to 100%, and a specificity ranging from 72% to 100%. The area under the curve across the studies demonstrated a range from 0.62 to 0.99.</p><p><strong>Conclusions: </strong>This scoping review highlights the potential of miRNA targets for diagnosing paediatric infections when studied rigorously. However, clinical translation is limited by poor adherence to STARD guidelines, lack of robust diagnostic metrics, and study heterogeneity. Many studies were set up with a case-control design, a design that, while highlighting differences, is more likely to identify non-specific biomarkers rather than those that are useful for novel clinical diagnostics.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 5","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12566583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145391720","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}
引用次数: 0
Long Non-Coding RNAs in Psoriasis: A Comprehensive Review of Expression Profiles, Mechanistic Insights, Genetic Associations, and Their Clinical Implications. 牛皮癣中的长链非编码rna:表达谱、机制见解、遗传关联及其临床意义的综合综述。
IF 3.6
Non-Coding RNA Pub Date : 2025-09-19 DOI: 10.3390/ncrna11050069
Judit Danis, Márta Széll
{"title":"Long Non-Coding RNAs in Psoriasis: A Comprehensive Review of Expression Profiles, Mechanistic Insights, Genetic Associations, and Their Clinical Implications.","authors":"Judit Danis, Márta Széll","doi":"10.3390/ncrna11050069","DOIUrl":"10.3390/ncrna11050069","url":null,"abstract":"<p><p>Psoriasis is a chronic inflammatory skin disorder affecting approximately 2% of the global population, characterized by abnormal keratinocyte proliferation and dysregulated immune responses. This review examines the emerging role of long non-coding RNAs (lncRNAs) in psoriasis pathogenesis, highlighting their significance as regulatory molecules in disease initiation, progression, and chronicity. LncRNAs demonstrate distinct expression patterns in psoriatic lesions, with upregulated transcripts such as MALAT1, XIST, MIR31HG, and HOTAIR promoting keratinocyte hyperproliferation, inhibiting apoptosis, and amplifying inflammatory cascades through mechanisms including microRNA sponging and transcription factor modulation. These molecules primarily target key signaling pathways including NF-κB, STAT3, and PI3K/AKT. Conversely, downregulated lncRNAs like NEAT1, MEG3, and PRINS normally function as tumor suppressor molecules that maintain epidermal homeostasis through pro-apoptotic and anti-inflammatory mechanisms. Their reduced expression contributes to the pathological hyperproliferative phenotype characteristic of psoriatic skin. Importantly, genetic variants within lncRNA loci have been identified as significant contributors to psoriasis susceptibility and treatment responses across different populations. Single- nucleotide polymorphisms in genes such as TRAF3IP2-AS1, HOTAIR, and CDKN2B-AS1 demonstrate population-specific associations with disease risk and therapeutic outcomes, suggesting their potential utility as pharmacogenomic markers. The complex regulatory networks involving lncRNAs provide new insights into psoriasis pathogenesis and offer promising avenues for personalized treatment strategies. Integration of lncRNA profiling into clinical practice may enhance our understanding of disease heterogeneity and improve therapeutic outcomes for psoriatic patients.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 5","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113962","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}
引用次数: 0
Role of Non-coding RNAs in Acute Myeloid Leukemia. 非编码rna在急性髓系白血病中的作用。
IF 3.6
Non-Coding RNA Pub Date : 2025-09-19 DOI: 10.3390/ncrna11050070
Shailendra S Maurya, Sarita Maurya, Sumit K Chaturvedi
{"title":"Role of Non-coding RNAs in Acute Myeloid Leukemia.","authors":"Shailendra S Maurya, Sarita Maurya, Sumit K Chaturvedi","doi":"10.3390/ncrna11050070","DOIUrl":"10.3390/ncrna11050070","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is a highly heterogeneous disease, with significantly higher incidence and fatality rates in the elderly. Even with recent decades of research progress in AML, the exact etiology of this deadly disease is still not fully understood, with recent advancements in sequencing technologies highlighting the role of a growing number of non-coding RNAs (ncRNAs) that are intimately associated with AML leukemogenesis. These ncRNAs have been found to have a significant role in leukemia-related cellular processes such as cell division, proliferation, and death. A few of these non-coding RNAs exhibit potential as prognostic biomarkers. The three main groups of ncRNAs that contribute unique activities, especially in cancer, are microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Their existence or altered expression levels frequently offer vital information on the diagnosis, course of treatment, and follow-up of cancer patients. The identification of ncRNAs has opened up new avenues for the diagnosis, prognosis, and therapy of acute myeloid leukemia. In order to provide a clear understanding of the significant influence that lncRNAs have on prognostic predictions and diagnostic accuracy in AML, this review aims to provide a comprehensive and insightful understanding of how these molecules actively participate in the complex landscape of the disease.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 5","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113944","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}
引用次数: 0
XIST Loss Induces Variable Transcriptional Responses Dependent on Cell States. XIST缺失诱导依赖于细胞状态的可变转录反应。
IF 3.6
Non-Coding RNA Pub Date : 2025-09-12 DOI: 10.3390/ncrna11050067
Dongning Chen, Ikrame Naciri, Jie Wu, Sha Sun
{"title":"XIST Loss Induces Variable Transcriptional Responses Dependent on Cell States.","authors":"Dongning Chen, Ikrame Naciri, Jie Wu, Sha Sun","doi":"10.3390/ncrna11050067","DOIUrl":"10.3390/ncrna11050067","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The X-inactivation specific transcript (XIST) is a long noncoding RNA playing a crucial regulatory role in X chromosome inactivation (XCI)-a transcriptional regulatory process that silences one of the two X chromosomes in females to ensure proper dosage compensation between male and female mammals. The transcription of <i>XIST</i> is maintained throughout a female's lifespan in all somatic cells, where XIST RNA binds to the X chromosome in <i>cis</i> and ensures chromosome-wide gene silencing. Disrupting <i>XIST</i> expression can lead to transcriptional reactivation of X-linked genes and epigenetic changes affecting cell development. The prevalence of XIST regulatory effects on mammalian transcription, however, remains unclarified. <b>Methods</b>: Here we performed a comparative expression analysis using RNA-sequencing datasets from recently published studies and examined the consequences of XIST-deletion on transcription at the whole genome, individual chromosome, and specific gene levels. We investigated the common differentially expressed genes (DEGs) and biological pathways following XIST loss across cell types, together with differential transcriptional analysis comparing the X chromosome and autosomes using cumulative distribution fractions. We analyzed the distribution of DEGs along the X chromosome with scatterplots and correlation analysis incorporating gene density and transposable elements. <b>Results</b>: Our findings indicate that the loss of XIST causes transcriptional changes in the X chromosome and autosomes that differ depending on cell type and state. XIST-deletion results in differential expression of genes subject to XCI-silencing as well as genes escaping XCI. In all the cell types we analyzed, X-linked genes show differential expression across the entire X chromosome in a cluster-like pattern according to gene density and, in certain cell types, correlate strongly with short interspersed nuclear element (SINE) distributions. <b>Conclusions</b>: Our results demonstrate that transcriptional roles of XIST can be highly associated with cell state: stem cells have different transcriptional responses compared to differentiated cells following XIST loss.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 5","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113956","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}
引用次数: 0
Chromatin-Associated RNAs Regulate Gene Expression and Chromatin Structure. 染色质相关rna调控基因表达和染色质结构。
IF 3.6
Non-Coding RNA Pub Date : 2025-09-12 DOI: 10.3390/ncrna11050068
Bingning Xie, Ann Dean
{"title":"Chromatin-Associated RNAs Regulate Gene Expression and Chromatin Structure.","authors":"Bingning Xie, Ann Dean","doi":"10.3390/ncrna11050068","DOIUrl":"10.3390/ncrna11050068","url":null,"abstract":"<p><p>Inside the eukaryotic nucleus, various RNAs are associated with chromatin. These include protein-coding pre-mRNA and different types of non-coding RNAs that are referred to as chromatin-associated RNAs (caRNAs). Recent studies have revealed the important roles of these caRNAs in regulating gene expression and chromatin interactions. In this review, we discuss the recent advances in understanding caRNAs. We first focus on their mode of action, then we summarize the methods used to detect caRNAs and categorize them into three classes: RNA-centric, DNA-centric and protein-centric. Finally, we turn to the proteins that mediate their functions.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 5","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114002","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}
引用次数: 0
Cellular Delivery of Functional AntimiR Conjugated to Bio-Produced Gold Nanoparticles. 功能性抗红外偶联生物金纳米颗粒的细胞递送。
IF 3.6
Non-Coding RNA Pub Date : 2025-09-11 DOI: 10.3390/ncrna11050066
Parastoo Pourali, Veronika Benson
{"title":"Cellular Delivery of Functional AntimiR Conjugated to Bio-Produced Gold Nanoparticles.","authors":"Parastoo Pourali, Veronika Benson","doi":"10.3390/ncrna11050066","DOIUrl":"10.3390/ncrna11050066","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Bio-produced gold nanoparticles (AuNPs) are effective carriers of short RNAs into specialized mammalian cells. Their potential application is still limited by scarce knowledge on their uptake and intracellular fate. Gold nanoparticles that are not biologically produced (NB-AuNPs) enter specialized cells primarily via clathrin-dependent endocytosis. Unlike the NB-AuNPs, the bio AuNPs possess natural surface coatings that significantly alter the AuNPs properties. Our research aimed to reveal the cellular uptake of the AuNPs with respect to delivering a functional RNA cargo. <b>Methods</b>: The AuNPs were conjugated with short inhibitory RNA specific to miR 135b. Mammary cancer cells 4T1 were pretreated with inhibitors of caveolin- and clathrin-mediated endocytosis and macropinocytosis. AuNPs' uptake, fate, and miR 135b knock-down were assessed with TEM and qPCR. <b>Results</b>: The AuNPs-antimiR 135b conjugates entered 4T1 cells via all the tested pathways and could be seen inside the cells in early and late endosomes as well as cytoplasm. In contrast to the clathrin-dependent pathway, the caveolae-mediated endocytosis and the macropinocytosis of the AuNPs resulted in the effective targeting and reduction of the miR 135b. <b>Conclusions</b>: The bio-produced AuNPs can effectively enter mammalian cells simultaneously by different endocytic pathways but the delivery of functional cargo is not achieved via the clathrin-dependent endocytosis.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 5","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114022","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}
引用次数: 0
Human-Specific Suppression of Hepatic Fatty Acid Catabolism by RNA-Binding Protein HuR. rna结合蛋白HuR对人特异性肝脂肪酸分解代谢的抑制作用。
IF 3.6
Non-Coding RNA Pub Date : 2025-09-01 DOI: 10.3390/ncrna11050065
Shohei Takaoka, Marcos E Jaso-Vera, Xiangbo Ruan
{"title":"Human-Specific Suppression of Hepatic Fatty Acid Catabolism by RNA-Binding Protein HuR.","authors":"Shohei Takaoka, Marcos E Jaso-Vera, Xiangbo Ruan","doi":"10.3390/ncrna11050065","DOIUrl":"10.3390/ncrna11050065","url":null,"abstract":"<p><p>RNA-binding proteins (RBPs) play essential roles in all major steps of RNA processing. Genetic studies in human and mouse models support that many RBPs are crucial for maintaining homeostasis in key tissues/organs, but to what extent the function of RBPs is conserved between humans and mice is not clear. Our recent study using a chimeric humanized liver mouse model found that knocking down human HuR in human hepatocytes resulted in a broad upregulation of human genes involved in fatty acid catabolism. This regulation is human-specific, as the knocking down of mouse HuR in the liver of traditional mouse models did not show these effects. To further study this human-specific role of HuR, we co-overexpressed HuR with PPARα, a master transcription factor that promotes fatty acid catabolism, in cultured cells. We found that HuR suppressed the expression of PPARα-induced fatty acid catabolism genes in human cells but not in mouse cells. We provide evidence supporting that the human-specific suppressive effect of HuR is independent of PPARα expression or location. The regulatory effects of HuR are also independent of its role in regulating mRNA stability. Using the human HMGCS2 gene as an example, we found that the suppressive effect of HuR cannot be explained by decreased promoter activity. We further provide evidence supporting that HuR suppresses the pre-mRNA processing of HMGCS2 gene, leading to accumulated intron/pre-mRNA expression of HMGCS2 gene. Furthermore, overexpression of HuR blocked and knocking down of HuR sensitized PPARα agonist-induced gene expression. By analyzing published RNA-seq data, we found compromised pre-mRNA processing for fatty acid catabolism genes in patients with fatty liver diseases, which was not observed in mouse fatty liver disease models. Our study supports the model that HuR suppresses the expression of fatty acid catabolism genes by blocking their pre-mRNA processing, which may partially explain the mild effects of PPARα agonists in treating fatty liver diseases in humans as compared with studies in mice.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 5","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113941","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}
引用次数: 0
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