Abstract
BackgroundPreeclampsia, 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.ResultsThe 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.ConclusionsOur 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.
Highlights
Preeclampsia, one of the major disorders of pregnancy, is characterized by inadequate trophoblast invasion and defective trophoblast-mediated remodeling of placental vasculature
We identified that MYC mRNA was a target of miR-34a in JEG-3 cells, and revealed that suppressing of MYC expression by miR-34a significantly inhibited JEG-3 invasion. These results suggest that miR-34a-mediated suppression of MYC expression may play a critical role in the regulation of trophoblast invasion and that excessive silencing may contribute to the pathogenesis of preeclampsia
Overexpression of miR-34a inhibited proliferation, migration and invasion of JEG-3 cells Human trophoblast cell line JEG-3 was transfected with miR-34a or non-targeting control (NC) expression vectors, and the level of miR-34a was remarkably elevated in the miR-34a-overexpressing cells compared with parental JEG-3 cells, whereas NC showed no effects on miR-34a expression (Fig. 2a)
Summary
Preeclampsia, one of the major disorders of pregnancy, is characterized by inadequate trophoblast invasion and defective trophoblast-mediated remodeling of placental vasculature. Understanding the molecular mechanisms underlying the pathogenesis of preeclampsia and searching for reliable early biomarkers are still the primary tasks for preeclampsia diagnosis and therapy. During early normal placental development, extravillous trophoblasts of fetal origin invade the uterine spiral arteries of the deciduas and myometrium, and remodel the placental vasculature in order to allow sufficient placental perfusion to nourish the fetus. Inadequate placental trophoblast invasion has been well documented in preeclampsia and it is generally believed to be the main cause for placental underperfusion and the development of preeclampsia [4, 1]. A number of genes that are associated with the invasiveness of carcinoma cells, such as matrix metalloproteinases and FOS transcription factors, have been demonstrated to play a role in trophoblast invasion in vitro [5, 6], yet a lot more remain to be explored
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