{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T19:33:47Z","timestamp":1769974427810,"version":"3.49.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Inflammatory Bowel Diseases (IBDs), encompassing Ulcerative Colitis (UC) and Crohn\u2019s Disease (CD), are chronic, recurrent inflammatory conditions of the gastrointestinal tract. The microRNA (miRNA) -mRNA regulatory network is pivotal in the initiation and progression of IBDs. Although individual studies provide valuable insights into miRNA mechanisms in IBDs, they often have limited scope due to constraints in population diversity, sample size, sequencing platform variability, batch effects, and potential researcher bias. Our study aimed to construct comprehensive miRNA-mRNA regulatory networks and determine the cellular sources and functions of key miRNAs in IBD pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To minimize potential bias from individual studies, we utilized a text mining-based approach on published scientific literature from PubMed and PMC databases to identify miRNAs and mRNAs associated with IBDs and their subtypes. We constructed miRNA-mRNA regulatory networks by integrating both predicted and experimentally validated results from DIANA, Targetscan, PicTar, Miranda, miRDB, and miRTarBase (all of which are databases for miRNA target annotation). The functions of miRNAs were determined through gene enrichment analysis of their target mRNAs. Additionally, we used two large-scale single-cell RNA sequencing datasets to identify the cellular sources of miRNAs and the association of their expression levels with clinical status, molecular and functional alternation in CD and UC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our analysis systematically summarized IBD-related genes using text-mining methodologies. We constructed three comprehensive miRNA-mRNA regulatory networks specific to IBD, CD, and UC. Through cross-analysis with two large-scale scRNA-seq datasets, we determined the cellular sources of the identified miRNAs. Despite originating from different cell types, hsa-miR-142, hsa-miR-145, and hsa-miR-146a were common to both CD and UC. Notably, hsa-miR-145 was identified as myofibroblast-specific in both CD and UC. Furthermore, we found that higher tissue repair and enhanced glucose and lipid metabolism were associated with hsa-miR-145 in myofibroblasts in both CD and UC contexts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This comprehensive approach revealed common and distinct miRNA-mRNA regulatory networks in CD and UC, identified cell-specific miRNA expressions (notably hsa-miR-145 in myofibroblasts), and linked miRNA expression to functional alterations in IBD. These findings not only enhance our understanding of IBD pathogenesis but also offer promising diagnostic biomarkers and therapeutic targets for clinical practice in managing IBDs.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1454532","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T04:47:12Z","timestamp":1724302032000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["The landscape of miRNA-mRNA regulatory network and cellular sources in inflammatory bowel diseases: insights from text mining and single cell RNA sequencing analysis"],"prefix":"10.3389","volume":"15","author":[{"given":"Yuan","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simeng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjac130","article-title":"Patients with inflammatory bowel disease have heterogeneous treatment preferences that are largely determined by the avoidance of abdominal pain and side effects [P-POWER IBD study]","volume":"17","author":"Louis","year":"2023","journal-title":"J Crohns Colitis"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2019-318264","article-title":"Anti-TNF therapy in IBD exerts its therapeutic effect through macrophage IL-10 signalling","volume":"69","author":"Koelink","year":"2020","journal-title":"Gut"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2016.208","article-title":"Current and emerging therapeutic targets for IBD","volume":"14","author":"Neurath","year":"2017","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"12445","DOI":"10.3390\/ijms232012445","article-title":"Etiology of IBD-is it still a mystery","volume":"23","author":"Kofla-Dlubacz","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nature22969","article-title":"Fine-mapping inflammatory bowel disease loci to single-variant resolution","volume":"547","author":"Huang","year":"2017","journal-title":"Nature"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/1073984","article-title":"Intestinal immune imbalance is an alarm in the development of IBD","volume":"2023","author":"Hu","year":"2023","journal-title":"Mediators Inflamm."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-021-00541-2","article-title":"Mycobiota-host immune interactions in IBD: coming out of the shadows","volume":"19","author":"Iliev","year":"2022","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.07.004","article-title":"PTPN2 regulates interactions between macrophages and intestinal epithelial cells to promote intestinal barrier function","volume":"159","author":"Spalinger","year":"2020","journal-title":"Gastroenterology"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.25122\/jml-2018-0075","article-title":"A review of the diagnosis, prevention, and treatment methods of inflammatory bowel disease","volume":"12","author":"Seyedian","year":"2019","journal-title":"J Med Life"},{"key":"B10","doi-asserted-by":"publisher","first-page":"7176","DOI":"10.3390\/ijms24087176","article-title":"Intestinal Microbiota and miRNA in IBD: A Narrative Review about Discoveries and Perspectives for the Future","volume":"24","author":"Oliveira","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2022.105996","article-title":"Identification of potential crucial genes and key pathways shared in Inflammatory Bowel Disease and cervical cancer by machine learning and integrated bioinformatics","volume":"149","author":"Nguyen","year":"2022","journal-title":"Comput Biol Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2019.09.007","article-title":"miRNAs as therapeutic targets in inflammatory disease","volume":"40","author":"Lu","year":"2019","journal-title":"Trends Pharmacol Sci"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.02.023","article-title":"MicroRNA-31 reduces inflammatory signaling and promotes regeneration in colon epithelium, and delivery of mimics in microspheres reduces colitis in mice","volume":"156","author":"Tian","year":"2019","journal-title":"Gastroenterology"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.7150\/thno.43716","article-title":"Parthenolide ameliorates colon inflammation through regulating Treg\/Th17 balance in a gut microbiota-dependent manner","volume":"10","author":"Liu","year":"2020","journal-title":"Theranostics"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2020.113394","article-title":"Qingchang Huashi Formula attenuates DSS-induced colitis in mice by restoring gut microbiota-metabolism homeostasis and goblet cell function","volume":"266","author":"Hu","year":"2021","journal-title":"J Ethnopharmacol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"101354","DOI":"10.1016\/j.jcmgh.2024.05.002","article-title":"SIRT1 stabilizes beta-trCP1 to inhibit snail1 expression in maintaining intestinal epithelial integrity to alleviate colitis","volume":"18","author":"Wang","year":"2024","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjac148","article-title":"Autophagy reduces the degradation and promotes membrane localization of occludin to enhance the intestinal epithelial tight junction barrier against paracellular macromolecule flux","volume":"17","author":"Saha","year":"2023","journal-title":"J Crohns Colitis"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2799-2","article-title":"A STAT3 palmitoylation cycle promotes T(H)17 differentiation and colitis","volume":"586","author":"Zhang","year":"2020","journal-title":"Nature"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.08.029","article-title":"Succinate produced by intestinal microbes promotes specification of tuft cells to suppress ileal inflammation","volume":"159","author":"Banerjee","year":"2020","journal-title":"Gastroenterology"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/database\/baw145","article-title":"Text mining resources for the life sciences","volume":"2016","author":"Przybyla","year":"2016","journal-title":"Database (Oxford)"},{"key":"B21","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1016\/j.drudis.2016.05.002","article-title":"Text mining patents for biomedical knowledge","volume":"21","author":"Rodriguez-Esteban","year":"2016","journal-title":"Drug Discov Today"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.4258\/hir.2017.23.3.141","article-title":"Text mining in biomedical domain with emphasis on document clustering","volume":"23","author":"Renganathan","year":"2017","journal-title":"Healthc Inform Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-9089-4_13","article-title":"Text mining for drug discovery","volume":"1939","author":"Zheng","year":"2019","journal-title":"Methods Mol Biol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/database\/baab031","article-title":"emiRIT: a text-mining-based resource for microRNA information","volume":"2021","author":"Roychowdhury","year":"2021","journal-title":"Database (Oxford)"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae235","article-title":"PubTator 3.0: an AI-powered literature resource for unlocking biomedical knowledge","author":"Wei","year":"2024","journal-title":"ArXiv"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.97","article-title":"Mapping identifiers for the integration of genomic datasets with the R\/Bioconductor package biomaRt","volume":"4","author":"Durinck","year":"2009","journal-title":"Nat Protoc"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz757","article-title":"miRDB: an online database for prediction of functional microRNA targets","volume":"48","author":"Chen","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"R90","DOI":"10.1186\/gb-2010-11-8-r90","article-title":"Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites","volume":"11","author":"Betel","year":"2010","journal-title":"Genome Biol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/ng1536","article-title":"Combinatorial microRNA target predictions","volume":"37","author":"Krek","year":"2005","journal-title":"Nat Genet"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav1741","article-title":"The biochemical basis of microRNA targeting efficacy","volume":"366","author":"McGeary","year":"2019","journal-title":"Science"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt393","article-title":"DIANA-microT web server v5.0: service integration into miRNA functional analysis workflows","volume":"41","author":"Paraskevopoulou","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1079","article-title":"miRTarBase update 2022: an informative resource for experimentally validated miRNA-target interactions","volume":"50","author":"Huang","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2021.100141","article-title":"clusterProfiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation (Camb)"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.01.002","article-title":"The landscape of immune dysregulation in Crohn\u2019s disease revealed through single-cell transcriptomic profiling in the ileum and colon","volume":"56","author":"Kong","year":"2023","journal-title":"Immunity"},{"key":"B35","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","article-title":"Dictionary learning for integrative, multimodal and scalable single-cell analysis","volume":"42","author":"Hao","year":"2024","journal-title":"Nat Biotechnol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"eaba1983","DOI":"10.1126\/sciadv.aba1983","article-title":"Single-cell RNA-seq reveals ectopic and aberrant lung-resident cell populations in idiopathic pulmonary fibrosis","volume":"6","author":"Adams","year":"2020","journal-title":"Sci Adv"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.06.029","article-title":"Intra- and inter-cellular rewiring of the human colon during ulcerative colitis","volume":"178","author":"Smillie","year":"2019","journal-title":"Cell"},{"key":"B38","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s13062-020-00280-5","article-title":"Pathophysiology of Crohn\u2019s disease inflammation and recurrence","volume":"15","author":"Petagna","year":"2020","journal-title":"Biol Direct"},{"key":"B39","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1038\/ncpgasthep0528","article-title":"Mechanisms of disease: pathogenesis of Crohn\u2019s disease and ulcerative colitis","volume":"3","author":"Sartor","year":"2006","journal-title":"Nat Clin Pract Gastroenterol Hepatol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2419","DOI":"10.1038\/s41467-021-22641-y","article-title":"MicroRNA-146a limits tumorigenic inflammation in colorectal cancer","volume":"12","author":"Garo","year":"2021","journal-title":"Nat Commun"},{"key":"B41","doi-asserted-by":"publisher","first-page":"296","DOI":"10.2119\/molmed.2014.00172","article-title":"miR-145 contributes to hypertrophic scarring of the skin by inducing myofibroblast activity","volume":"21","author":"Gras","year":"2015","journal-title":"Mol Med"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1007\/s10863-023-09980-9","article-title":"Bidirectional negative feedback actions of DNMT3A and miR-145 in regulating autophagy in cardiac fibroblasts and affecting myocardial fibrosis","volume":"55","author":"Xu","year":"2023","journal-title":"J Bioenerg Biomembr"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.910884","article-title":"The epigenetic role of miRNAs in endocrine crosstalk between the cardiovascular system and adipose tissue: A bidirectional view","volume":"10","author":"Soci","year":"2022","journal-title":"Front Cell Dev Biol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-021-06725-y","article-title":"The role of microRNAs in diseases and related signaling pathways","volume":"49","author":"Vaghf","year":"2022","journal-title":"Mol Biol Rep"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2023.03.230","article-title":"Low-dose interleukin 2 for the treatment of moderate to severe ulcerative colitis","volume":"165","author":"Allegretti","year":"2023","journal-title":"Gastroenterology"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aav1080","article-title":"IL-23 and IL-2 activation of STAT5 is required for optimal IL-22 production in ILC3s during colitis","volume":"5","author":"Bauche","year":"2020","journal-title":"Sci Immunol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"e0185097","DOI":"10.1371\/journal.pone.0185097","article-title":"Inhibition of miR-142-5P ameliorates disease in mouse models of experimental colitis","volume":"12","author":"Duijvis","year":"2017","journal-title":"PloS One"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1159\/000528312","article-title":"Molecular basis of intestinal fibrosis in inflammatory bowel disease","volume":"7","author":"Andoh","year":"2023","journal-title":"Inflamm Intest Dis"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-219493","article-title":"miR-145 regulates myofibroblast differentiation and lung fibrosis","volume":"27","author":"Yang","year":"2013","journal-title":"FASEB J"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-015-2110-0","article-title":"The myofibroblast, a key cell in normal and pathological tissue repair","volume":"73","author":"Darby","year":"2016","journal-title":"Cell Mol Life Sci"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.103846","article-title":"Hypermethylation of miR-145 promoter-mediated SOX9-CLDN8 pathway regulates intestinal mucosal barrier in Crohn\u2019s disease","volume":"76","author":"Zhuang","year":"2022","journal-title":"EBioMedicine"},{"key":"B52","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s12943-019-0977-3","article-title":"MiR155 sensitized B-lymphoma cells to anti-PD-L1 antibody via PD-1\/PD-L1-mediated lymphoma cell interaction with CD8+T cells","volume":"18","author":"Zheng","year":"2019","journal-title":"Mol Cancer"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2023-329963","article-title":"Fibrosis in IBD: from pathogenesis to therapeutic targets","volume":"73","author":"Rieder","year":"2024","journal-title":"Gut"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1454532\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T04:47:15Z","timestamp":1724302035000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1454532\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,22]]},"references-count":53,"alternative-id":["10.3389\/fimmu.2024.1454532"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1454532","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,22]]},"article-number":"1454532"}}