MicroRNA-576-5p enhances the invasion ability of trophoblast cells in preeclampsia by targeting TFAP2A

Background: Preeclampsia (PE) is a common pregnancy-related syndrome characterized by hypertension and proteinuria, and a major cause of maternal mortality. Therefore, there is an urgent need to identify early biomarkers of PE. The aim of the present study was to identify the functions of miR-576-5p in PE.

Methods: Effects of miR-576-5p and transcription factor AP-2α (TFAP2A) on invasion of human trophoblast HTR8/SVneo cells were investigated. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to assess the expression of miR-576-5p, TFAP2A, E-cad, and Vimentin in PE tissues and cells. Additionally, immunofluorescence was used to detect the expression of TFAP2A in PE trophoblastic tissue. Subsequently, constructed miR-576-5p mimics, miR-576-5p inhibitor, and siRNA-TFAP2A plasmids were transfected into HTR8/SVneo cells for further experiments, including a CCK-8 assay for cell proliferation, Transwell assay for cell invasion and the luciferase reporter gene system was employed for target verification.

Results: A lower expression of miR-576-5p and a higher expression of TFAP2A were identified in PE rats. E-cadherin was highly expressed while Vimentin was downregulated. Further statistical analysis indicated that cell proliferation of HTR8/SVneo cells decreased in the miR-576-5p inhibitor group and increased in the miR-576-5p mimics and siRNA-TFAP2A groups. miR-576-5p inhibitor suppressed cell invasion, and miR-576-5p mimics and siRNA-TFAP2A improved cell invasion. The analysis of luciferase reporter demonstrated a decreased luciferase activity in miR-576-5p mimics group compared with control group, which indicates that TFAP2A may be a target of miR-576-5p. Interference of TFAP2A could downregulate E-cadherin and upregulate Vimentin expression.

Conclusion: Overexpression of miR-576-5p and knockdown of TFAP2A may elevate cell proliferation and invasion of human trophoblast cells in vitro. Therefore, miR-576-5p may be used as a notable biomarker for the diagnosis, prevention, and treatment of PE. miR-576-5p targeting TFAP2A deserve further investigation in order to explore their potential role in PE.