miR-377 inhibition enhances the survival of trophoblast cells via upregulation of FNDC5 in gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is a metabolic dysregulation closely related to both obesity and type 2 diabetes; however, the molecular mechanism underlying GDM is still unclear. The purpose of this study was to investigate the effects of microRNA-377 (miR-377-3p) and fibronectin type III domain containing 5 (FNDC5) in regulating the cell growth of trophoblasts under high glucose (HG) conditions during the development of GDM. Serum miR-377-3p was upregulated and positively correlated with fasting blood glucose level in GDM patients. miR-377-3p downregulation increased the cell vitality and suppressed the cell apoptosis of HG-treated HTR-8/SVneo and BeWo cells. Using TargetScan prediction, luciferase assay, and western blot, it was found that miR-377-3p could target FNDC5 and suppress its expression. However, FNDC5 downregulation abolished the effect of miR-377-3p inhibitor in HTR-8/SVneo cells. Together, miR-377 is a potential target for GDM biomarker, which promotes cell growth and suppresses cell apoptosis, partly through the upregulation of FNDC5.