MicroRNA-204 suppresses trophoblast-like cell invasion by targeting matrix metalloproteinase-9.

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.