MicroRNA-431 affects trophoblast migration and invasion by targeting ZEB1 in preeclampsia

Preeclampsia (PE) is a pregnancy complication that is characterized by higher blood pressure, together with higher protein quantity presence in the urine, which occurs after 20 weeks of gestation leading to severity of adverse maternal and fetal consequences. Some special microRNAs (miRNAs) expressed in placentas may be related to the occurrence of PE. Researchers have found that the expression of miR-431 in PE placentas was increased if compared with normal placentas; however, the effect and mechanism of miR-431 in PE are still unknown.

In this study, we compared the expression levels of miR-431 and its putative target gene Zinc finger E-box-binding homeobox 1 (ZEB1) in 30 PE placentas and 30 normal placenta tissues. The effects of miR-431 and ZEB1 were verified by CCK-8 assay, transwell migration and invasion assay, cell cycle distribution assay and apoptosis assay in HTR-8/SVneo cells transfected with miR-431 mimic, siR-ZEB1 and their negative controls.

Results revealed that miR-431 was markedly added, while the mRNA and protein expressions of ZEB1 were decreased in PE placentas. The functional tests showed over-expression of miR-431 suppressed ZEB1 expression and decreased the migration and invasive capacity of trophoblast cells. MiR-431 overexpression induced apoptosis of HTR-8/SVneo cells, but it had no significant effect on cell proliferation and the distribution of cell cycle. In addition, siR-ZEB1 simulated the roles of miR-431 mimic. We found that miR-431 mimic and siR-ZEB1 reduced the epithelial-mesenchymal transition (EMT) with added E-cadherin expression and reduced vimentin expression in the cell line.

In conclusion, we found that miR-431 inhibited the migration and invasion of trophoblastic cells by targeting ZEB1, which might give rise to the onset of PE.