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Our previous research findings demonstrated that neonatal mice infected with CV-A6 exhibited limb weakness, paralysis, and ultimately succumbed to death. However, the underlying mechanism of CV-A6-induced nervous system injury remains elusive. Numerous reports have highlighted the pivotal role of miRNAs in various viral infections.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Separately established infection and control groups of mice were used to create miRNA profiles of the brain tissues before and after CV-A6 transfection, followed by experimental verification, prediction, and analysis of the results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At 2 days post-infection (dpi), 4 dpi, and 2dpi vs 4dpi, we identified 175, 198 and 78 significantly differentially expressed miRNAs respectively using qRT-PCR for validation purposes. Subsequently, we predicted target genes of these differentially expressed miRNAs and determined their potential targets through GO (Gene Ontology) enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis. Finally, we verified the miRNA-mRNA pairing via double luciferase experiments while confirming functional enrichment of target genes through Western Blotting analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The results from this study suggest that transcriptional regulation, neuronal necrosis, pro-inflammatory cytokine release, and antiviral immunity are all implicated in the pathogenesis of central nervous system injury in mice infected with CV-A6. Brain injury resulting from CV-A6 infection may involve multiple pathways, including glial cell activation, neuronal necrosis, synaptic destruction, degenerative diseases of the nervous system. It can even encompass destruction of the blood-brain barrier, leading to central nervous system injury. The dysregulated miRNAs and signaling pathways discovered in this study provide valuable insights for further investigations into the pathogenesis of CV-A6.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2024.1405689","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T05:10:50Z","timestamp":1724303450000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Analysis of miRNAs involved in mouse brain injury upon Coxsackievirus A6 infection"],"prefix":"10.3389","volume":"14","author":[{"given":"Yihao","family":"Sun","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yilin","family":"Hao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shasha","family":"Qian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuo","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuting","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1017\/neu.2016.47","article-title":"Inflammatory aspects of epileptogenesis: contribution of molecular inflammatory mechanisms","volume":"29","author":"Alyu","year":"2017","journal-title":"Acta neuropsychiatrica."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/v10080440","article-title":"The diverse roles of microRNAs at the host (-) virus interface","volume":"10","author":"Bernier","year":"2018","journal-title":"Viruses"},{"key":"B3","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.nbd.2015.10.002","article-title":"Prospects for mTOR-mediated functional repair after central nervous system trauma","volume":"85","author":"Berry","year":"2016","journal-title":"Neurobiol. diseas."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1586\/14787210.2015.1058156","article-title":"Coxsackievirus A6: a new emerging pathogen causing hand, foot and mouth disease outbreaks worldwide","volume":"13","author":"Bian","year":"2015","journal-title":"Expert Rev. anti-infective Ther."},{"key":"B5","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/S1672-0229(08)60044-3","article-title":"A brief review on the mechanisms of miRNA regulation","volume":"7","author":"Cai","year":"2009","journal-title":"Genomics Proteomics Bioinf."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2023.105432","article-title":"The 2022 outbreak and the pathobiology of the coxsackie virus [hand foot and mouth disease] in India","volume":"111","author":"Chavan","year":"2023","journal-title":"Infection Genet. evolution."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2583","DOI":"10.1016\/j.cellsig.2014.07.017","article-title":"miR-709 inhibits 3T3-L1 cell differentiation by targeting GSK3\u03b2 of Wnt\/\u03b2-catenin signaling","volume":"26","author":"Chen","year":"2014","journal-title":"Cell. signalling"},{"key":"B8","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.neuint.2016.12.007","article-title":"Targeting antioxidant enzyme expression as a therapeutic strategy for ischemic stroke","volume":"107","author":"Davis","year":"2017","journal-title":"Neurochemistry Int."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1038\/s41379-019-0285-x","article-title":"DNA methylation-based classification of sinonasal undifferentiated carcinoma","volume":"32","author":"Dogan","year":"2019","journal-title":"Modern Pathol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1080\/1040841X.2018.1499608","article-title":"miRNAs in enterovirus infection","volume":"44","author":"Engelmann","year":"2018","journal-title":"Crit. 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