Hypoxia Induces Down-regulation Of MiR-1246 In Trophoblast Cells Via Targeting CCNG2 And Its Role In The Pathogenesis Of Preeclampsia

Backgorund:Preeclampsia is responsible for the increase risk in perinatal morbidity and mortality worldwide.Numerous studies have confirmed that miRNAs can participate in the pathogenesis of preeclampsia by regulating the expression of target genes.This study aimed to investigate "Hypoxia-miR-1246-CCNG2" axis in preeclampsia progression and the underlying mechanism.Methods:The differential miRNAs between the preeclampsia and the normal pregnancies were screened out through bioinformatics analysis.MiR-1246 was screened out and enrichment analysis of its target genes were carried out for further prediction of its function.MiR-1246 and cycling G2 expression in placental tissues was detected by RT-qPCR and western blotting.Pearson correlation analysis between the expression of miR-1246 and CCNG2 in placenta,and the patient’s clinical parameters were carried out.Hypoxia-induced trophoblast cell model was established.Cell migration and invasion were detected by wound healing assay and transwell assay.Cell proliferation was measured by CCK-8,while cell apoptosis was detected by flow cytometry via the double-staining of Annexin V-FITC/Propidium Iodide.The interaction between miR-1246 and CCNG2 was proved by luciferase reporter assay.Results:MiR-1246 was screened out by bioinformatics analysis,and CCNG2,as one of its predicted target genes,was selected as the research object.Expression of miR-1246 and CCNG2 reflected the severity of preeclampsia to a certain extent.Hypoxia altered the expression of miR-1246 and CCNG2.MiR-1246 promote migration,invasion and proliferation while inhibited apoptosis in trophoblast cells under normal and hypoxic conditions.Knocking down of CCNG2 improved the function of trophoblasts to a certain extent.Furthermore,miR-1246 can make a role play by binding with the 3’UTR of CCNG2.Conclusions:The expression of miR-1246 was closely related to the severity of preeclamptic patients.Changes in the hypoxia-miR-1246-CCNG2 axis restored the cellular functional impairment due to oxidative stress.It was expected to be a new biomarker and potential therapeutic target for preeclampsia.