MicroRNA-30a contributes to pre-eclampsia through regulating the proliferation, apoptosis, and angiogenesis modulation potential of mesenchymal stem cells by targeting AVEN

Abstract

ABSTRACT Pre-eclampsia (PE) is a pregnancy-associated disease related to an unprecedented hypertension attack. Mesenchymal stem cells (MSCs) play a crucial role in PE pathology. . Our research was designed to illustrate the functions of microRNA-30a (miR-30a) in proliferation, apoptosis, and the potential of regulating angiogenesis in MSCs, and to analyze its potential molecular mechanisms. TargetScan software and the luciferase reporter assay were used to forecast and verify the relationship between miR-30a and AVEN. MiR-30a and AVEN expression in the decidual tissue and decidua (d)MSCs of healthy pregnant women and PE patients were assessed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Cell proliferation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide (MTT), flow cytometry, and transwell assays were used to evaluate cell proliferation, growth, the cell cycle, apoptosis, and migration. Furthermore, the tube formation ability was evaluated using the human umbilical vein endothelial cell (HUVEC) tube formation assay. AVEN is the target gene of miR-30a. MiR-30a was upregulated in decidual tissues and dMSCs of PE patients. However, AVEN was weakly expressed, and AVEN expression was negatively related to miR-30a levels in decidual tissues and dMSCs of PE patients. Compared to the mimic control group, upregulation of miR-30a inhibited dMSC proliferation and cell growth, promoted G0/G1 phase arrest, and induced apoptosis. Furthermore, the miR-30a mimic transfected dMSC culture supernatant suppressed HTR-8/SVneo cell migration ability and HUVEC tube formation ability. However, AVEN reversed these changes. In conclusion, miR-30a/AVEN may serve as a new axis for PE treatment.