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In our previous study, miR-26a-5p was identified as one of the seven miRNAs whose levels were elevated in plasma samples from women with pregnancies complicated by severe PE (sPE). Defects in human extravillous trophoblast (EVT) invasion and migration contribute to the pathogenesis of early-onset PE; however, the effects of miR-26a-5p on these processes remain unclear. In this study, an increase in miR-26a-5p levels in plasma and placenta samples from pregnancies complicated by early-onset sPE was first confirmed. A progressive decrease in miR-26a-5p expression during the differentiation of cytotrophoblasts into invasive EVTs within trophoblast columns was revealed by fluorescence in situ hybridization. A mimic and an inhibitor of miR-26a-5p significantly suppressed or promoted, respectively, the invasion and migration of HTR-8\/SVneo cells and the outgrowth of primary EVTs derived from placental villous explants. Actin related protein 2\/3 complex subunit 3 (ARPC3) was identified as a direct target of miR-26a-5p, and knockdown of ARPC3 mimicked the effects of miR-26a-5p on HTR-8\/SVneo cell invasion\/migration and explant EVT outgrowth. Conversely, ectopic expression of ARPC3 alleviated the suppressive effects of miR-26a-5p overexpression on HTR-8\/SVneo cell invasion and migration. Disruption of actin cytoskeletal organization was observed following ARPC3 knockdown, leading to a significant transformation of lamellipodia to filopodia at the leading edges of cells, which eventually impeded directional EVT invasion and migration. Thus, dysregulated actin cytoskeletal organization caused by overactive miR-26a-5p\/ARPC3 axis may contribute to the pathogenesis of early-onset sPE by impairing EVT invasion and migration.<\/jats:p>","DOI":"10.1093\/biolre\/ioaf151","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T07:23:46Z","timestamp":1751873026000},"page":"1219-1236","source":"Crossref","is-referenced-by-count":1,"title":["Human extravillous trophoblast invasion and migration are impeded by excessive miR-26a-5p: dysregulated actin cytoskeleton in extravillous trophoblasts during early-onset severe preeclampsia"],"prefix":"10.1093","volume":"113","author":[{"given":"Yuanke","family":"Zheng","sequence":"first","affiliation":[{"name":"Reproductive Medical Center, the First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan ,","place":["China"]},{"name":"Henan Key Laboratory of Reproduction and Genetics, the First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan ,","place":["China"]},{"name":"Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, the First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Liang","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center, the First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan ,","place":["China"]},{"name":"Henan Key Laboratory of Reproduction and Genetics, the First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan ,","place":["China"]},{"name":"Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, the First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyue","family":"Li","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center, the First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan ,","place":["China"]},{"name":"Henan Key Laboratory of Reproduction and Genetics, the First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan ,","place":["China"]},{"name":"Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, the First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianfei","family":"Feng","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center, the First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan ,","place":["China"]},{"name":"Henan Key Laboratory of Reproduction and Genetics, the First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan ,","place":["China"]},{"name":"Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, the First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohe","family":"Lei","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center, the First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan ,","place":["China"]},{"name":"Henan Key Laboratory of Reproduction and Genetics, the First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan ,","place":["China"]},{"name":"Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, the First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haotian","family":"Lu","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center, the First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan ,","place":["China"]},{"name":"Henan Key Laboratory of Reproduction and Genetics, the First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan ,","place":["China"]},{"name":"Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, the First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7299-3978","authenticated-orcid":false,"given":"Liang","family":"Wu","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center, the First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan ,","place":["China"]},{"name":"Henan Key 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