Non-coding RNA Research最新文献

{"title":"Upregulation of LINC02154 promotes esophageal cancer progression by enhancing cell cycling and epithelial-mesenchymal transition","authors":"Kotoha Shimote ,&nbsp;Takeshi Niinuma ,&nbsp;Hiroshi Kitajima ,&nbsp;Kazuya Ishiguro ,&nbsp;Eiichiro Yamamoto ,&nbsp;Gota Sudo ,&nbsp;Akira Yorozu ,&nbsp;Mutsumi Toyota ,&nbsp;Masahiro Kai ,&nbsp;Masashi Idogawa ,&nbsp;Hiromu Suzuki","doi":"10.1016/j.ncrna.2025.06.001","DOIUrl":"10.1016/j.ncrna.2025.06.001","url":null,"abstract":"<div><div>Long noncoding RNAs (lncRNAs) play crucial roles in the progression of human malignancies; however, their involvement in esophageal cancer (ESCA) remains incompletely understood. In this study, we screened for lncRNAs upregulated in ESCA and identified 12 lncRNAs significantly upregulated in primary ESCA tumors. Among those, elevated LINC02154 expression correlated positively with advanced T stages. LINC02154 knockdown in ESCA cell lines suppressed cell proliferation and migration, while ectopic expression of LINC02154 enhanced colony formation. Depletion of LINC02154 suppressed genes involved in various oncogenic processes, including cell cycling, epithelial-mesenchymal transition (EMT), and metabolism. We also found that LINC02154 promotes EMT and enhances chemoresistance, at least in part, through suppression of miR-200b. Finally, RNA-pulldown and mass spectrometry analysis revealed that LINC02154 interacts with proteins involved in the cornified envelope or desmosome. These findings suggest that LINC02154 exerts oncogenic effects through modulation of multiple oncogenic signaling pathways in ESCA and that LINC02154 is a potential therapeutic target.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 107-116"},"PeriodicalIF":5.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the multifaceted role of circular RNA in aging: from molecular mechanisms to therapeutic potentials","authors":"Yang Wang ,&nbsp;Cong Wang ,&nbsp;Xin Dai ,&nbsp;Ge Liu ,&nbsp;Xiaolong Gao ,&nbsp;Junru Zhang","doi":"10.1016/j.ncrna.2025.05.015","DOIUrl":"10.1016/j.ncrna.2025.05.015","url":null,"abstract":"<div><div>Aging is an inevitable physiological process that occurs in living organisms and has significant implications for health and disease. As the human lifespan extends, the functionality of organs gradually diminishes, leading to the emergence of various aging-related symptoms. While it is not feasible to completely halt the aging process, investigating key molecules involved in aging can help devise valid strategies to delay its progression. Circular RNAs (circRNAs) are a novel category of non-protein-coding RNAs and are abundant in cells. Their distinctive circular structure and diverse biological functions have garnered considerable attention from the scientific community. CircRNAs play a crucial role in regulating biological processes such as the cell cycle, apoptosis, and autophagy. They are implicated in various mechanisms, including cell signaling, influencing post-transcriptional regulation, and functioning as sponges for microRNAs (miRNAs), to modulate gene expression and impact cellular senescence. This research paper sets out to elucidate the mechanisms by which circRNAs regulate gene expression, epigenetic modifications, and cellular functions, as well as to assess their potential applications in aging-associated disorders.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 129-144"},"PeriodicalIF":5.9,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144254875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA-29a-5p attenuates hemorrhagic transformation and improves outcomes after mechanical reperfusion for acute ischemic stroke","authors":"Chang-Luo Li ,&nbsp;Jin-Kun Zhuang ,&nbsp;Zhong Liu ,&nbsp;Zhong-Run Huang ,&nbsp;Chun Xiang ,&nbsp;Qian-Yu Chen ,&nbsp;Ze-Xin Chen ,&nbsp;Zhong-Song Shi","doi":"10.1016/j.ncrna.2025.05.016","DOIUrl":"10.1016/j.ncrna.2025.05.016","url":null,"abstract":"<div><h3>Background</h3><div>Hemorrhage transformation (HT) following endovascular reperfusion treatment is associated with worse clinical outcomes in acute ischemic stroke patients. MicroRNA (miR) modulates several aspects of cerebral ischemia-reperfusion injury, including blood-brain barrier (BBB) integrity, inflammation, oxidative stress, and apoptosis, significantly impacting cerebral recovery and function. This study investigated the role of astrocytic miR-29a-5p in HT in the transient middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation reoxygenation (OGD/R) model of astrocytes.</div></div><div><h3>Methods</h3><div>MiR-29a-5p expression in the OGD/R astrocyte model was assessed. The astrocyte injury, the expression of A1 and A2 phenotypes of reactive astrocytes, and the regulation of miR-29a-5p target genes were evaluated after the miR-29a-5p intervention. A mechanical reperfusion-induced HT model was established in hyperglycemic rats using 5-h MCAO following reperfusion at 6 h. MiR-29a-5p agomir was administered intravenously before reperfusion. Infarct volume, HT, BBB damage, neurological score, the expression of miR-29a-5p, and its target genes were evaluated.</div></div><div><h3>Results</h3><div>MiR-29a-5p expression decreased in OGD/R-treated astrocytes and the peri-infarction tissue and blood of the MCAO model. Elevating miR-29a-5p levels reduced astrocyte injury, suppressed neurotoxic A1 astrocyte markers (C3, Fkbp5, and Serping1), while enhanced neuroprotective A2 astrocyte markers (S100a10 and Emp1) in the OGD/R and MCAO models. Intravenous administration of miR-29a-5p agomir increased the expression of miR-29a-5p and reduced infarct volume, reperfusion-induced HT, and BBB breakdown after ischemia, improving neurological outcomes in the MCAO model. Overexpression of miR-29a-5p effectively suppressed the expression of its direct target genes, glycogen synthase kinase 3 beta and aquaporin 4 in the OGD/R and MCAO models.</div></div><div><h3>Conclusions</h3><div>MiR-29a-5p alleviates astrocyte injury and regulates A1 and A2 astrocyte markers, glycogen synthase kinase 3 beta, and aquaporin 4 in astrocytes subjected to ischemia-reperfusion injury. Astrocytic miR-29a-5p may be a protective target for reducing HT and improving outcomes following mechanical reperfusion in acute ischemic stroke.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 96-106"},"PeriodicalIF":5.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA MEG3/CTCF-CXCR4 axis functions in the regulation of breast cancer cell migration","authors":"Gusai Elhassan ,&nbsp;Xiangxue Bu ,&nbsp;Jiaxin Liu ,&nbsp;Shuai Hou ,&nbsp;Jinsong Yan ,&nbsp;Haixin Lei","doi":"10.1016/j.ncrna.2025.05.014","DOIUrl":"10.1016/j.ncrna.2025.05.014","url":null,"abstract":"<div><div>Loss or decreased expression of lncRNA MEG3 is a frequent event in the progression of many different malignancies. Overexpression of MEG3 in breast cancer cell lines MCF7 or MDA-MB-231 prevented cell migration, whereas depletion of MEG3 in human mammary epithelial cell line MCF10A strikingly promoted cell migration. As RNA-protein interactions are vital for RNA to function, RNP assembled on MEG3 <em>in vivo</em> was purified using affinity purification followed by mass spectrometry, which revealed ∼600 proteins with the potential to interact with MEG3. Bioinformatic analysis on RNA-seq data from MCF7 with MEG3 overexpression and MCF10A with MEG3 depletion led to the identification of CXCR4 as the major downstream mediator negatively regulated by MEG3 that facilitated breast cancer cell migration. In addition, the chromatin regulator CTCF emerged as the MEG3-binding protein that might regulate CXCR4 expression after comparison of proteins presenting in MEG3 lncRNP to ChIP-seq data and GPSAdb data of CXCR4. Further evidence was provided to show CTCF upregulated the expression of CXCR4 at transcriptional level, whereas co-expression of MEG3 with CTCF abolished transcriptional activation of CXCR4. Overall, our study pinpoints the importance of MEG3/CTCF-CXCR4 axis in regulating migration of breast cancer cells and provides novel insight into the mechanism of lncRNA MEG3 in cancer development.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 117-128"},"PeriodicalIF":5.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncPTEN1, a long non-coding RNA generated from PTEN, suppresses lung cancer metastasis through the regulation of EMT progress","authors":"Zichu Shen ,&nbsp;Ailin Zhong ,&nbsp;Chun Zhang ,&nbsp;Xiaowei Tang ,&nbsp;Xuyang Zhao ,&nbsp;Zhiyuan Hou ,&nbsp;Hui Liang ,&nbsp;Yuxin Yin","doi":"10.1016/j.ncrna.2025.05.011","DOIUrl":"10.1016/j.ncrna.2025.05.011","url":null,"abstract":"<div><div>Lung cancer is among the most frequently observed and lethal malignancies globally, and metastasis represents a critical determinant of patient outcomes. PTEN, a well-established tumor suppressor, has emerged as an important regulator in lung cancer progression. However, the molecular mechanism of <em>PTEN</em> gene suppressing lung cancer metastasis lacks deeper exploration. In this research, we identify and characterize LncPTEN1, a novel long non-coding RNA generated from <em>PTEN</em> gene. We show that YTHDC1 promotes the alternative splicing of LncPTEN1, resulting in significantly elevated LncPTEN1 expression in normal lung cells. Clinical analyses across multiple patient cohorts demonstrate that low LncPTEN1 expression strongly correlates with poor patient survival and increased metastasis, indicating its potential as a prognostic biomarker. Mechanistically, LncPTEN1 facilitates the interaction between Trim16 and Vimentin, promoting the ubiquitination and proteasomal degradation of Vimentin, thereby suppressing EMT-driven metastasis. The collective evidence from our investigation demonstrates that LncPTEN1 represents a novel tumor-suppressive lncRNA which inhibits lung cancer metastasis through promoting the degradation of Vimentin and inhibiting the EMT progress.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 25-37"},"PeriodicalIF":5.9,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The multifaceted role of microRNAs in colorectal cancer: pathogenesis and therapeutic implications","authors":"Federica Longo ,&nbsp;Giuseppe Gattuso ,&nbsp;Graziana Spoto ,&nbsp;Daria Ricci ,&nbsp;Anastasia Cristina Venera Vitale ,&nbsp;Alessandro Lavoro ,&nbsp;Saverio Candido ,&nbsp;Massimo Libra ,&nbsp;Luca Falzone","doi":"10.1016/j.ncrna.2025.05.012","DOIUrl":"10.1016/j.ncrna.2025.05.012","url":null,"abstract":"<div><div>MicroRNAs (miRNAs) are important regulators of gene expression and their dysregulation is involved in various diseases, including tumors. Among these, colorectal cancer (CRC) is the result of both genetic and epigenetic alterations with miRNAs playing a key pathogenetic role. Although numerous studies have investigated the most frequently dysregulated miRNAs in CRC, there is still no consensus on the specific role of individual miRNAs in the mechanisms leading to tumorigenesis, tumor progression, and the development of chemoresistance. This lack of clarity highlights the need for a deeper understanding of miRNA functions in CRC. Therefore, this review aims to clarify the role of miRNAs in CRC by examining their involvement in major oncogenic pathways, highlighting key miRNAs implicated in the disease, and exploring their potential as diagnostic biomarkers and therapeutic targets. By providing a comprehensive overview, we hope to shed light on the complex and multifaceted roles of miRNAs in CRC, which could pave the way for more effective CRC monitoring and the development of miRNA-guided therapeutic strategies.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 65-95"},"PeriodicalIF":5.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-92a-1-5p contributes to cellular proliferation and survival in chronic myeloid leukemia and its inhibition enhances imatinib efficacy","authors":"Joanne Peters ,&nbsp;Emeline Bollaert ,&nbsp;Anne-Sophie Cloos ,&nbsp;Melissa Claus ,&nbsp;Ahmed Essaghir ,&nbsp;Sandrine Lenglez ,&nbsp;Pascale Saussoy ,&nbsp;Guillaume Dachy ,&nbsp;Pierre Autin ,&nbsp;Jean-Baptiste Demoulin ,&nbsp;Violaine Havelange","doi":"10.1016/j.ncrna.2025.05.008","DOIUrl":"10.1016/j.ncrna.2025.05.008","url":null,"abstract":"<div><div>Tyrosine kinase inhibitors (TKI), such as imatinib, have revolutionized chronic myeloid leukemia (CML) treatment. Despite this success, TKI intolerance and resistance remain significant clinical challenges. A promising therapeutic approach is to simultaneously target the <em>BCR::ABL1</em> oncogene and other oncogenic drivers. The polycistronic <em>miR-17-92</em> cluster is known to contribute to CML development and progression, but the specific roles of <em>miR-92a-1-5p</em> within this cluster remain unclear. In this study, we assess the roles of this microRNA and evaluate the therapeutic potential of combining microRNA inhibition with imatinib to improve treatment outcome. Our results show that <em>miR-92a-1-5p</em> is downregulated by imatinib in myeloid cell lines harboring <em>BCR::ABL1</em> and in CML patient samples. Inhibition of <em>miR-92a-1-5p</em> reduces proliferation and enhances imatinib-induced cell death, while its overexpression increases proliferation and counteracts the effects of imatinib on cell death. This decrease in proliferation caused by <em>miR-92a-1-5p</em> inhibition is rescued after simultaneous inhibition of two newly identified target genes: <em>BNIP3L (NIX)</em> and <em>TP53INP1</em>. We confirm that <em>miR-92a-1-5p</em> regulates proliferation and cell cycle by targeting <em>TP53INP1</em> and decreases autophagy by targeting <em>BNIP3L</em>. Our data suggest that <em>miR-92a-1-5p</em> plays a role in CML progression, and its inhibition enhances imatinib anti-leukemic efficacy, making it a potential therapeutic target.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 14-24"},"PeriodicalIF":5.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational discovery of conserved RNA structures and functional characterization of a structured lncRNA in Leishmania braziliensis","authors":"Caroline R. Espada ,&nbsp;Christian Anthon ,&nbsp;Rubens D.M. Magalhães ,&nbsp;José Carlos Quilles Junior ,&nbsp;Natalia M.M. Teles ,&nbsp;Fabiano S. Pais ,&nbsp;Lissur A. Orsine ,&nbsp;Letícia de Almeida ,&nbsp;Tânia P.A. Defina ,&nbsp;Adam Dowle ,&nbsp;Jan Gorodkin ,&nbsp;Pegine B. Walrad ,&nbsp;Angela K. Cruz","doi":"10.1016/j.ncrna.2025.05.010","DOIUrl":"10.1016/j.ncrna.2025.05.010","url":null,"abstract":"<div><div><em>Leishmania</em> parasites alternate between hosts, facing environmental changes that demand rapid gene expression adaptation. Lacking canonical RNA polymerase II promoters, transcription in these eukaryotes is polycistronic, with gene regulation occurring post-transcriptionally. Although non-coding RNAs (ncRNAs) have been identified in <em>Leishmania</em> transcriptomes, their functions remain unclear. Recognizing RNA structure's importance, we performed a genome-wide alignment of <em>L. braziliensis</em> and related species, identifying conserved RNA structures, 38 of which overlap with known ncRNAs. One such ncRNA, <em>lncRNA45</em>, was functionally characterized. Using a knockout cell line, we demonstrated that <em>lncRNA45</em> is crucial for parasite fitness. Reintroducing the wild type <em>lncRNA45</em> restored fitness, while a version with a single nucleotide substitution in the structured region did not. This mutation also altered RNA-protein interactions. These findings suggest that <em>lncRNA45</em>'s regulatory role and protein interactions rely on its secondary structure. This study highlights the significance of structured lncRNAs in <em>Leishmania</em> biology and their potential as therapeutic targets. Further research into these ncRNAs could uncover new parasite regulation mechanisms and inspire novel treatment strategies.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 51-64"},"PeriodicalIF":5.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosome-derived hsa_circ_0007132 promotes lenvatinib resistance by inhibiting the ubiquitin-mediated degradation of NONO","authors":"Mingbo Cao ,&nbsp;Yuxuan Li ,&nbsp;Xiaorui Su ,&nbsp;Yongchang Tang ,&nbsp;Feng Yuan ,&nbsp;Yupeng Ren ,&nbsp;Meihai Deng ,&nbsp;Zhicheng Yao","doi":"10.1016/j.ncrna.2025.05.007","DOIUrl":"10.1016/j.ncrna.2025.05.007","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a highly heterogeneous solid tumor, with its incidence showing a troubling upward trend over the past decade. Lenvatinib is one of the first-line medications for treating advanced HCC, however, the development of resistance significantly undermines its potential to improve patient prognosis. In recent years, exosomal circRNAs have been implicated in the resistance mechanisms of various cancers, yet their role in mediating lenvatinib resistance (LR) remains largely unexplored. In this study, we identified hsa_circ_0007132, which is upregulated in the serum exosomes of HCC patients exhibiting progressive disease (PD) following lenvatinib treatment. Subsequently, we employed LR cell lines to conduct both <em>in vitro</em> and <em>in vivo</em> experiments, which provided compelling evidence that hsa_circ_0007132 significantly promotes LR in HCC. Mechanistically, hsa_circ_0007132 interacts with the NONO protein, impairing its ubiquitination and leading to increased stability and upregulation of NONO expression, thereby enhancing NONO-mediated nuclear export of ZEB1 mRNA and elevating ZEB1 protein expression, which ultimately contributes to LR. In summary, our findings unveil a critical mechanism through which HCC mediates tumor progression and LR via exosomal hsa_circ_0007132, while also emphasizing that targeting NONO may represent a promising therapeutic strategy to overcome LR.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 1-13"},"PeriodicalIF":5.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Ocrelizumab in modulating gene and microRNA expression in multiple sclerosis","authors":"Bruna De Felice ,&nbsp;Elisabetta Signoriello ,&nbsp;Concetta Montanino ,&nbsp;Giuseppe Romano ,&nbsp;Deborah Archetto ,&nbsp;Elisabetta Maida ,&nbsp;Martina Marciano ,&nbsp;Simona Bonavita ,&nbsp;Giacomo Lus ,&nbsp;Federica Farinella ,&nbsp;Cinzia Coppola","doi":"10.1016/j.ncrna.2025.05.009","DOIUrl":"10.1016/j.ncrna.2025.05.009","url":null,"abstract":"<div><div>Multiple sclerosis is an autoimmune neurodegenerative disease and one of the most significant challenges in modern neurology, impacting approximately 2.8 million people globally. As a multifactorial condition, susceptibility to MS can result from a combination of genetic and environmental factors. Current treatment strategies aim to prevent acute attacks, slow disease progression, and alleviate symptoms. Ocrelizumab, a monoclonal antibody targeting CD20, has demonstrated efficacy in clinical trials by reducing both disease activity and frequency of relapses.</div><div>Given the recent approval of this treatment, we investigated whether Ocrelizumab alters the expression of key miRNAs and genes involved in neuroinflammation, such as let-7a-5p, miR-14a-5p, miR-21a-5p, miR-338-3p, IL-1, IL-6, NEAT1, NEFL, NESTIN, SLC16A10 and TNF-alpha, by comparing their expression in patients’ blood before and after one year of treatment with Ocrelizumab. Additionally, we explored potential inverse correlations and direct or indirect interactions among the genes and miRNAs that showed significant changes in expression. Lastly, we conducted a pathway analysis to understand the overall effects potentially exerted by the drug.</div><div>Results revealed a significant decrease in the expression of TNF-alpha, SLC16A10, NEFL and IL-6, and an increase in let-7a-5p expression. There was an inverse correlation between let-7a-5p and the four genes, while the genes positively correlated with each other, suggesting let-7a-5p as a common modulator. These findings indicate that further investigation is needed to determine if the drug directly upregulates let-7a-5p, thereby downregulating the four genes, or if these expression changes are an indication of an overall reduction in inflammation.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"13 ","pages":"Pages 174-183"},"PeriodicalIF":5.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}