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We aimed to explore the effects of let\u20107d on trophoblast proliferation, migration, invasion and apoptosis in PE and its underlying mechanism. Placental tissues were collected from PE patients and healthy pregnant women, and it was found that let\u20107d expression was increased, while KDM3A and ENO2 expression was decreased in PE tissues and cells. Bioinformatics analysis indicated the interaction among let\u20107d, KDM3A and ENO2, confirmed by dual luciferase reporter gene assay; ChIP experiment identified methylated modification to ENO2 by KDM3A. With gain\u2010 and loss\u2010function method, silencing of let\u20107d increased KDM3A expression and enhanced the binding between KDM3A and ENO2. Furthermore, overexpression of let\u20107d suppressed cell proliferation, migration and invasion of trophoblasts, and induced apoptosis of trophoblasts, while these capacities were restored upon additional treatment of overexpressed ENO2. PE rat models were established to explore the effects of let\u20107d and ENO2 on PE in vivo. The results established that the silencing of let\u20107d alleviated the tissue injury and PE\u2010related symptoms when reducing urine protein, TUNEL\u2010positive cells and increasing ENO2, and KDM3A expression in rats. Cumulatively, let\u20107d suppressed cell progression of trophoblasts, and induced apoptosis through the down\u2010regulation of KDM3A to promote ENO2 methylation, thereby promoting progression of PE. Such an epigenetic network of let\u20107d, KDM3A and ENO2 in the pathogenesis of PE might provide novel insight into targeted therapy against this disorder.<\/jats:p>","DOI":"10.1111\/jcmm.16299","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T07:54:52Z","timestamp":1628150092000},"page":"8127-8139","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Overexpression of let\u20107d explains down\u2010regulated KDM3A and ENO2 in the pathogenesis of preeclampsia"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0612-2319","authenticated-orcid":false,"given":"Qian","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Obstetrics Linyi People\u2019s Hospital Linyi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghui","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Obstetrics Linyi People\u2019s Hospital Linyi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics Linyi People\u2019s Hospital Linyi 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