{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T13:31:34Z","timestamp":1777037494306,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:00:00Z","timestamp":1666137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005047","name":"Natural Science Foundation of Liaoning Province","doi-asserted-by":"publisher","award":["2021\u2010MS\u201001"],"award-info":[{"award-number":["2021\u2010MS\u201001"]}],"id":[{"id":"10.13039\/501100005047","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Preeclampsia (PE) is an obstetric disorder. N6\u2010methyladenosine (m6A) modification is related to PE trophoblast biological behaviors. This study explored the mechanism of m6A\u2010modified circSETD2 in trophoblast biological behaviors. Chorionic trophoblast apoptosis and circSETD2 expression in PE rat models were detected. HTR8\/SVneo cells were induced by CoCl<jats:sub>2<\/jats:sub> to establish PE trophoblast models. circSETD2 was silenced or overexpressed to evaluate its effect on cell proliferation, invasion, and apoptosis. m6A level of circSETD2 in trophoblasts was changed by pcDNA3.1\u2010METTL3 and pcDNA3.1\u2010FTO. The targeting relations among miR\u2010181a\u20105p, circSETD2, and MCL1 were verified by dual\u2010luciferase assay. miR\u2010181a\u20105p and MCL1 expressions were interfered with to confirm the effect of m6A\u2010modified circSETD2. m6A methylation level was changed in PE rats for in vivo validation. PE rats showed diminished circSETD2 expression and increased apoptosis index. circSETD2 overexpression promoted trophoblast proliferation and invasion, and reduced apoptosis. METTL3 overexpression increased total m6A, circSETD2 m6A, and circSETD2 levels. m6A modification mediated circSETD2 upregulation. circSETD2 was a sponge of miR\u2010181a\u20105p to elevate MCL1 transcription. miR\u2010181a\u20105p overexpression or MCL1 silencing annulled the role of m6A\u2010modified circSETD2. circSETD2 inhibition negated suppression of METTL3 overexpression on chorionic trophoblast apoptosis in vivo. Collectively, m6A modification of circSETD2 suppressed miR\u2010181a\u20105p and increased MCL1 transcription, thus regulating trophoblasts.<\/jats:p>","DOI":"10.1002\/tox.23683","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T17:09:41Z","timestamp":1666199381000},"page":"422-435","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["<scp>N6<\/scp>\u2010methyladenosine modification in trophoblasts promotes <scp>circSETD2<\/scp> expression, inhibits <scp>miR<\/scp>\u2010181a\u20105p, and elevates <scp>MCL1<\/scp> transcription to reduce apoptosis of trophoblasts"],"prefix":"10.1002","volume":"38","author":[{"given":"Dan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Shengjing Hospital of China Medical University  Shenyang Liaoning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbo","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Shengjing Hospital of China Medical University  Shenyang Liaoning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Shengjing Hospital of China Medical University  Shenyang Liaoning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guiyu","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Shengjing Hospital of China Medical University  Shenyang Liaoning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2847-5182","authenticated-orcid":false,"given":"Yajun","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and 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