Study On Mechanisms Of MicroRNA-210 Participate In Tne Occurrence Of Preeclampsia

Complicating 7%-10% pregnancy, preeclampsia (PE) is a pregnancy-specific syndrome manifested by the onset of hypertension and proteinuria after the 20th week of gestation. Abnormal placenta development has been generally accepted as the initial cause of the disorder. Up to now, many researchers have been demonstrated that lots of miRNAs abnormally express in preeclamptic placenta and peripheral blood plasma, indicating this small molecule participated in the occurrence of preeclampsia. Recently, microRNA-210 (miR-210) has been found to be upregulated in preeclamptic placentas compared with normal placentas, indicating a possible association of this small molecule with the placental pathology of preeclampsia. However, the function of miR-210 in the development of the placenta remains elusive. The aim of this study was to characterize the molecular mechanism of preeclampsia development by examining the role of miR-210.In this study, miR-210, thrombospondin type I domain containing 7A(THSD7A), potassium channel modulatory factor 1 (KCMF1) expressions were compared in placentas from healthy pregnant individuals and patients with preeclampsia, and the role of miR-210 in trophoblast cell invasion via the downregulation of KCMF1 and THSD7A were investigated in the immortal trophoblast cell line HTR8/SVneo. The levels of KCMF1 and THSD7A were significantly lower in preeclamptic placenta tissues than in gestational week-matched normal placentas, which were inversely correlated with the level of miR-210. KCMF1 and THSD7A were validated as the direct targets of miR-210 using bioinformatics prediction, real-time polymerase chain reaction, Western blotting, and dual luciferase assay in HTR8/SVneo cells. MiR-210 inhibited the invasion of trophoblast cells, and this inhibition was abrogated by the overexpression of KCMF1. MiR-210 inhibitor promoted the invasion of trophoblast cells, and this promotion was abrogated by the THSD7A specific siRNA. The inflammatory factor tumor necrosis factor-α(TNFα) could upregulate miR-210 while suppressing KCMF1 expression in HTR8/SVneo cells. Hypoxia could induce the expression of miR-210 but inhibite the expression of THSD7A.The findings in this study indicate that aberrant miR-210 expression may contribute to the occurrence of preeclampsia by interfering with KCMF1- and THSD7A-mediated signaling in the human placenta. This study provides a new way of thinking to further explore the pathogenesis of preeclampsia.