MicroRNA-513c-5p is involved in the pathogenesis of preeclampsia by regulating of low-density lipoprotein receptor-associated protein 6

Abstract

BackgroundPreeclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality. Studies on the role of microRNAs (miRNAs), in the pathogenesis of PE through their effects on trophoblast function have been reported, but roles for some miRNAs including miR-513c-5p, have not been identified. We aimed to evaluate potential miRNA candidates that regulate the LRP6 mRNAand to elucidate the possible mechanism in PE. Potential miRNAs were selected by bioinformatics analysis, PCR of placenta tissues and dual luciferase reporter assay of HTR-8/SVneo cells.MethodsA bioinformatics analysis (Gene Expression Omnibus, GEO; miRWalk) was performed to screen the possible miRNAs that participate in the pathology of PE. Placentas from patients with PE and women with a normal pregnancy were collected to detect the expression of predicted miRNAs by RT-qPCR. A dual luciferase reporter assay was used to test the binding of the potential miRNAs to LRP6. The effects of miR-513c-5p on the biological functions of HTR-8/SVneo cells were further evaluated by performing EdU staining, flow cytometry, wound healing assays and Transwell assays.ResultsGEO and miRWalk predicted 16 miRNAs that might target LRP6. Hsa-miR-371a-5p, hsa-miR-513c-5p, hsa-miR-126-3p, hsa-miR-145-5p, hsa-miR-193b-5p and hsa-miR-296-5p were 6 miRNAs upregulated in the PE placenta. LRP6 was downregulated in patients with PE compared to normal women. miR-513c-5p mimics inhibited LRP6 expression in HTR-8/SVneo cells, and LRP6 is the target gene of miR-513c-5p. miR-513c-5p mimics also inhibited invasion, migration and proliferation of HTR-8/SVneo cells but promoted their apoptosis.ConclusionsOur study reveals that overexpression of placenta miR-513c-5p is involved in PE by regulating the biological functions of trophoblasts through the inhibition of LRP6.