Downregulated miR-195 Detected in Preeclamptic Placenta Affects Trophoblast Cell Invasion via Modulating ActRIIA Expression

• Published in: PloS one Vol. 7; no. 6; p. e38875
• Main Authors: Bai, Yang, Yang, Weiwei, Yang, Hui-xia, Liao, Qinping, Ye, Gang, Fu, Guodong, Ji, Lei, Xu, Peng, Wang, Hao, Li, Yu-xia, Peng, Chun, Wang, Yan-ling
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.06.2012; Public Library of Science (PLoS)
• Subjects: Aberration; Activin; Activin Receptors, Type II - genetics; Activin Receptors, Type II - metabolism; Adult; Angiogenesis; Assaying; Biology; Blood pressure; Breast cancer; Cell cycle; Cell Line; Comparative analysis; Cyclin D1 - genetics; Cyclin D1 - metabolism; Cyclin D3 - genetics; Cyclin D3 - metabolism; Epigenetics; Evolutionary biology; Female; Gene Expression; Gene Expression Regulation; Genes; Gestation; Gynecology; Humans; Hypertension; Laboratories; Medicine; MicroRNAs; MicroRNAs - genetics; Obstetrics; Pathogenesis; Placenta; Placenta - metabolism; Placenta - pathology; Pre-eclampsia; Pre-Eclampsia - genetics; Preeclampsia; Pregnancy; Pregnant women; Proteinuria; Ribonucleic acid; RNA; Signal transduction; Signaling; Tissues; Trophoblasts - metabolism; Trophoblasts - pathology; Western blotting; Young Adult; Zoology; Beijing China; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0038875

Preeclampsia (PE) is a pregnancy-specific syndrome manifested by on-set of hypertension and proteinuria after 20 weeks of gestation. Abnormal placenta development has been generally accepted as initial cause of the disorder. Recently, miR-195 was found to be down-regulated in preeclamptic placentas compared with normal pregnant ones, indicating possible association of this small molecule with placental pathology of preeclampsia. By far the function of miR-195 in the development of placenta remains unknown. Bioinformatic assay predicted ActRIIA as one of the targets for miR-195. By using Real-time PCR, Western blotting and Dual Luciferase Assay, we validated that ActRIIA was the direct target of miR-195 in human trophoblast cells. Transwell insert invasion assay showed that miR-195 could promote cell invasion in trophoblast cell line, HTR8/SVneo cells, and the effect could be abrogated by overexpressed ActRIIA. In preeclamptic placenta tissues, pri-miR-195 and mature miR-195 expressions were down-regulated, whereas ActRIIA level appeared to be increased when compared with that in gestational-week-matched normal placentas. This is the first report on the function of miR-195 in human placental trophoblast cells which reveals an invasion-promoting effect of the small RNA via repressing ActRIIA. Aberrant expression of miR-195 may contribute to the occurrence of preeclampsia through interfering with Activin/Nodal signaling mediated by ActRIIA in human placenta.