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The expression levels of HDAC4, microRNA (miR)\u2010134\u20105p, and forkhead box protein M1 (FOXM1) in placentas from PE patients and healthy controls and their correlations were examined. HTR8\/SVneo cells were cultured and underwent gene intervention. Then, trophoblast proliferation, invasion, and migration were evaluated by 5\u2010ethynyl\u20102\u02b9deoxyuridine, Transwell, and scratch assays. The enrichments of HDAC4 and acetylated histone H3 at lysine 9 (H3K9Ac) on the miR\u2010134\u20105p promoter were quantified by chromatin immunoprecipitation. The binding of miR\u2010134\u20105p to FOXM1 was analyzed by dual\u2010luciferase assay. HDAC4 and FOXM1 were downregulated while miR\u2010134\u20105p was upregulated in PE placentas. HDAC4 downregulation impaired trophoblast proliferation, invasion, and migration while HDAC4 overexpression played the opposite role. Mechanically, HDAC4 deacetylated H3K9Ac to repress miR\u2010134\u20105p expression by erasing H3K9Ac, reduced the binding of miR\u2010134\u20105p to FOXM1, and then promoted FOXM1 transcription. miR\u2010134\u20105p overexpression or FOXM1 downregulation abrogated the promotive role of HDAC overexpression in trophoblast invasion and migration. Our study unraveled a novel mechanism of trophoblast proliferation, invasion, and migration and proposed that HDAC4 may be a promising target for the treatment of PE.<\/jats:p>","DOI":"10.1002\/mrd.23706","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T18:11:42Z","timestamp":1695924702000},"page":"849-860","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["HDAC4 regulates the proliferation, migration, and invasion of trophoblasts in pre\u2010eclampsia through the miR\u2010134\u20105p\/FOXM1 axis"],"prefix":"10.1002","volume":"90","author":[{"given":"Yanli","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Beijing Ditan Hospital Affiliated Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodi","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of 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