MiRNA-320a inhibits trophoblast cell invasion by targeting estrogen-related receptor-gamma

AimMicroRNAs (miRs) play an essential role in the modulation of trophoblast function. We explored miR-320a expression in the human placenta. In addition, we report the promising effect and target functional loop of miR-320a in trophoblasts. MethodsMiR-320a expression was investigated in both pre-eclamptic and healthy placenta tissues by quantitative real time-polymerase chain reaction to determine how miR-320a affected invasion, proliferation and migration in trophoblasts. A lipopolysaccharide (LPS) model was established in trophoblasts to reveal how LPS supplementation stimulated miR-320a expression. Western blot was applied to measure protein expression, which was involved in pathways modulated by miR-320a in pre-eclamptic placentas. ResultsMiR-320a expression was enhanced in the placental specimens of pre-eclamptic patients. Excessive miR-320a expression remarkably suppressed trophoblast invasion but did not affect migration or proliferation. However, transfection with miR-320a inhibitor reinforced trophoblast invasion in vitro. Luciferase assays verified that estrogen-related receptor-gamma (ERR) served as a direct target of miR-320a. Quantitative real-time polymerase chain reaction and Western blot demonstrated that excessive miR-320a expression downregulated ERR transcription and translation. Additionally, LPS supplementation showed excessive miR-320a expression and ERR downregulation. Impaired ERR and enhanced miR-320a expression occurred in PE placentas compared to controls. Pearson correlation and linear regression analysis revealed that miR-320a expression was negatively related to ERR expression in normal and pre-eclamptic placentas. ConclusionsThese findings indicate that miR-320a overexpression causes anomalous placentation by targeting ERR. Our research reveals the promising effect of miR-320a and the ERR functional loop on placentation.