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Transcriptomic data analysis and experimental verification confirmed a downregulation of ACVR2A expression in placental tissues from PE patients. In this study, CRISPR\/Cas9 technology was employed to investigate the effect of ACVR2A gene deletion on trophoblast cells using the HTR8\/SVneo and JAR cell lines. Deletion of ACVR2A inhibits trophoblastic migration, proliferation, and invasion, underscoring its pivotal role in cellular function. RNA-seq data analysis unveiled an intricate regulatory network influenced by ACVR2A gene knockout, especially in the TCF7\/c-JUN pathway. By employing RT-PCR and immunohistochemical analysis, a potential association between ACVR2A and the TCF7\/c-JUN pathway was hypothesized and confirmed. The complexity of PE onset and the significance of genetic factors were emphasized, particularly the role of the ACVR2A gene identified in genome-wide association study. This study established a robust foundation for delving deeper into the intricate mechanisms of PE, paving the way for focused early intervention, personalized treatment, and enhanced obstetric healthcare.<\/jats:p>","DOI":"10.7554\/elife.101236","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T08:26:14Z","timestamp":1736151974000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.101236","source":"Crossref","is-referenced-by-count":1,"title":["ACVR2A facilitates trophoblast cell invasion through TCF7\/c-JUN pathway in pre-eclampsia progression"],"prefix":"10.7554","volume":"14","author":[{"given":"Shujing","family":"Yang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00zat6v61","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Obstetrics and Gynecology, Obstetrics; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine; 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