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Widespread N6\u2010methyladenosine (m6A) modifications on mRNAs have been found to be involved in various biological processes. However, the role of m6A modification in the pathogenesis of FGR remains elusive. Here, we report that elevated levels of METTL3 and m6A modification were detected in FGR placentae. Functionally, cell migration, invasion, and proliferation abilities were suppressed after METTL3 overexpression in HTR8\/SVneo cells. Subsequently, methylated RNA immunoprecipitation sequencing (MeRIP\u2010seq) and RNA sequencing (RNA\u2010seq) of METTL3\u2010knockdown HTR8\/SVneo cells were utilized together to identify FOSL1 as the downstream target genes of METTL3. Furthermore, we illustrated that METTL3\u2010mediated m6A modification enhanced the expression of FOSL1 in a IGF2BP2 dependent manner. FOSL1 inhibited trophoblast invasion and migration. Importantly, STM2457, a novel METTL3 catalytic inhibitor, was intravenously administered to FGR mice models, which restore fetal and placental weights in\u00a0vivo. In\u00a0vitro STM2457 regulated trophoblast proliferation, invasion, and migration in a dose\u2010dependent manner. In summary, this study reveals that METTL3 and IGF2BP2 increase FOSL1 expression in an m6A\u2010dependent manner. The increase of FOSL1disrupts normal trophoblast invasion, which results in the progression of FGR. METTL3 can serve as a potential target for FGR therapy.<\/jats:p>","DOI":"10.1096\/fj.202401665r","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T10:50:40Z","timestamp":1732099840000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<scp>METTL3<\/scp>\n                    and\n                    <scp>IGF2BP2<\/scp>\n                    coordinately regulate\n                    <scp>FOSL1 mRNA<\/scp>\n                    via\n                    <scp>m6A<\/scp>\n                    modification, suppressing trophoblast invasion and contributing to fetal growth restriction"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2373-9445","authenticated-orcid":false,"given":"Ruixin","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics West China Second University Hospital, Sichuan University  Chengdu 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