MicroRNA-30a-3p is overexpressed in the placentas of patients with preeclampsia and affects trophoblast invasion and apoptosis by its effects on IGF-1

Abstract

Objective: Preeclampsia (PE) affects many women globally and remains a primary cause of neonatal and maternal morbidity and mortality. Aberrant placental microRNA (miRNA) expression might be associated with PE. Previously, 33 PE-related miRNAs, 11 up-regulated and 23 down-regulated, were detected in placentas of women with severe PE when compared with those of normal patients. One of the most up-regulated miRNAs in PE is miR-30a-3p. The predicted target of it is insulin-like growth factor 1 (IGF-1), which has been reported to have a relatively low expression level in PE patients. This study was conducted to determine the aberrant increased of miR-30a-3p in the placentas of women with preeclampsia and to elucidate the target and function of it in trophoblast cells.

Study design: miR-30a-3p expression in placenta tissues was compared between women with preeclampsia (n = 25) and normal pregnant women (n = 20). The miRNA target was studied by in silico and functional assay. The effects of the miRNA were verified by apoptosis assay and invasion assay in the trophoblast cell line.

Results: miR-30a-3p was increased significantly in the placenta of women with preeclampsia when compared to those with normal pregnancies. Luciferase assay confirmed direct regulation of miR-30a-3p on the expression of IGF-1. Forced expression of miR-30a-3p suppressed IGF-1 protein expression in the HTR-8/SVneo cells. The functional assay suggests that the over-expression of miR-30a-3p alter the invasive capacity of JEG-3 cells and induce the apoptosis of HTR-8/SVneo cells (Figure).

Conclusion: Expression of miR-30a-3p was significantly increased in the placentas of patients with preeclampsia. miR-30a-3p might be involved in the pathogenesis of preeclampsia by targeting IGF-1 and regulating the invasion and apoptosis of trophoblast cells.

Keywords: IGF-1; apoptosis; epigenetics; functional assays; invasion; microRNA; placenta; preeclampsia; trophoblast.