MicroRNA-34a inhibits human trophoblast cell invasion by targeting MYC

Abstract

Background: Preeclampsia, one of the major disorders of pregnancy, is characterized by inadequate trophoblast invasion and defective trophoblast-mediated remodeling of placental vasculature. MicroRNA-34a (miR-34a) has been found to be aberrantly expressed in the placentas of preeclamptic patients, yet its role in placental development and in the pathogenesis of preeclampsia remains elusive. Results: The levels of miR-34a in the placentas of 20 preeclamptic patients and 20 healthy subjects were determined by real time-PCR, and miR-34a was found significantly elevated in the preeclamptic placentas. Further, the function of miR-34a in trophoblast cells was investigated by overexpressing miR-34a in JEG-3 trophoblast cell line. Overexpression of miR-34a in JEG-3 cells inhibited cell proliferation, migration and invasion. In addition, elevated expression of miR-34a reduced the expression of both endogenous and ectopic MYC. Moreover, we identified that MYC mRNA was a direct target of miR-34a in JEG-3 cells by dual luciferase reporter assay, and found that downregulation of MYC expression by miR-34a targeting significantly reduced the invasiveness of JEG-3 cells. Conclusions: Our findings provide preliminary evidence for the diverse functions of miR-34a in trophoblast biology, and suggest that miR-34a suppresses trophoblast invasion by directly targeting MYC.