miR‑424‑5p is downregulated in the placentas of patients with preeclampsia and affects trophoblast migration and invasion

Abstract

Insufficient invasion of trophoblast cells has been reported to be closely associated with the pathogenesis of preeclampsia (PE). MicroRNAs (miRs) have essential roles in the trophoblasts invasion via targeting specific genes with diverse functions. However, the underlying mechanism remains largely unclear and requires further investigation. The present study aimed to identify and evaluate the potential functions of miRs in trophoblasts invasion and to reveal the underlying mechanisms. In the present study, differentially expressed miRs that were screened based on previously published microarray data (GSE96985) and a significantly downregulated miR-424-5p (miR-424) was chosen for further investigation. Subsequently, reverse transcription-quantitative PCR, CCK-8, apoptosis, wound healing and Transwell assays were performed to determine the cell viability, apoptotic rate, cell migration and invasion of trophoblast cells. The results showed that miR-424 was decreased in placenta specimens from patients with PE. Upregulation of miR-424 promoted cell viability, suppressed cell apoptosis and improved the invasion and migration of trophoblasts, whereas inhibition of miR-424 had opposite results. Adenomatous polyposis coli (APC), a key mediator of Wnt/β-catenin signaling pathway, was identified as a functional target of miR-424 and an inverse relationship was observed between APC and miR-424 in placenta specimens. Further investigations revealed that APC overexpression efficiently suppressed the effect of miR-424 in trophoblast cells. In addition, the miR-424-mediated effects on trophoblast cells were dependent on the promotion of Wnt/β-catenin signaling pathway. The present findings revealed that miR-424 regulates the trophoblast cell invasion by regulating Wnt/β-catenin pathway through targeting APC, indicating miR-424 as a potential candidate for the treatment of PE.