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However, the role of m6A methyltransferase Wilms' tumor 1\u2010associated protein (WTAP) in regulating microglial polarization during ischemic stroke (IS) remains unknown. We performed bioinformatics analysis to identify m6A\u2010related differentially expressed genes in IS and validated these genes in a mouse middle cerebral artery occlusion model and a BV2 cell oxygen\u2010glucose deprivation\/reperfusion model. We found that microglial m6A modification was increased, and that WTAP was the most significantly differentially expressed m6A regulator during IS. High expression of WTAP is closely correlated with microglia\u2010mediated neuroinflammation in IS. Mechanistically, WTAP promoted m6A modification, which promoted prostaglandin endoperoxide synthase\u20102 (PTGS2) by enhancing its mRNA stability. WTAP promoted M1 microglial polarization by elevating PTGS2 expression via m6A modification of PTGS2 mRNA in the oxygen\u2010glucose deprivation\/reperfusion model. In conclusion, WTAP is a crucial posttranscriptional regulator that contributes to post\u2010IS neuroinflammation. WTAP knockdown confers cerebral protection by shifting the microglial phenotype from M1 to M2, primarily by reducing PTGS2 mRNA stability in an m6A\u2010dependent manner.<\/jats:p>","DOI":"10.1002\/cbin.12266","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T09:49:20Z","timestamp":1734428960000},"page":"288-302","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Wilms' tumor 1\u2010associated protein aggravates ischemic stroke by promoting M1 polarization of microglia by enhancing PTGS2 mRNA stability in an m6A\u2010dependent manner"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1472-3052","authenticated-orcid":false,"given":"Haijing","family":"Sui","sequence":"first","affiliation":[{"name":"Department of Anesthesiology The Second Affiliated Hospital of Harbin Medical University Harbin China"},{"name":"Heilongjiang Province Key Laboratory of 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