title: MicroRNA-204 suppresses trophoblast-like cell invasion by targeting matrix metalloproteinase-9.
abstract: Preeclampsia is a devastating pregnancy-related syndrome characterized by the onset of hypertension, proteinuria and edema. Insufficient invasion of trophoblasts is well-known to be correlated with preeclampsia development. The present study was performed to investigate the functional role microRNA (miRNA)-204 in trophoblastic invasion in vitro. We here found that the invasive capabilities of BeWo and JEG3 trophoblast-like cells were suppressed by miR-204 mimics, whereas enhanced by its inhibitor. Matrix metalloproteinase-9 (MMP9) was first confirmed to play a role in regulating trophoblast invasion through loss- or gain-of-function experiment. Notably, we demonstrated MMP9 as a direct target of miR-204 in BeWo cells by using the dual-luciferase assay. Moreover, forced overexpression of MMP9 was noted to partly attenuate the inhibitory effects of miR-204 on BeWo cell invasion. Taken together, our study indicates that miR-204 may contribute to the development of preeclampsia by inhibiting trophoblastic invasion, and that MMP9 is involved in miR-204-mediated trophoblast cell invasion. Our study suggests miR-204 as a novel therapeutic target for preeclampsia.
authors.affiliation: Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China. Electronic address: hongboguan@126.com.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Guan
mesh_terms: D002460:Cell Line; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D011225:Pre-Eclampsia / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism / Q000473:pathology*
chemical_list: C549404:MIRN204 microRNA, human; D035683:MicroRNAs; D020780:Matrix Metalloproteinase 9
keywords: Invasion; MMP9; Preeclampsia; Trophoblast; miR-204