The miRNA-29b Is Downregulated in Placenta During Gestational Diabetes Mellitus and May Alter Placenta Development by Regulating Trophoblast Migration and Invasion Through a HIF3A-Dependent Mechanism

Abstract

Gestational diabetes mellitus (GDM) is a disease that changes the function of microvascular of placenta. MicroRNA (miRNA) expression in placenta may contribute to the pathogenesis of GDM. Here, we evaluate the role and function of <i>miR-29b</i> in the development of GDM. This study discovered that <i>miR-29b</i> expression was lower in placentas derived from patients with GDM than that in control placentas. <i>MiR-29b</i> over-expression inhibited cell growth and migration, and <i>miR-29b</i> knockdown promoted cell migration. Then we predicted and confirmed that <i>HIF3A</i> was a direct target of <i>miR-29b</i> with two specific binding sites at the recognition sequences of <i>miR-29b</i> in 3'-UTR of <i>HIF3A</i> mRNA, which was negatively correlated with <i>miR-29b</i> expression level. The up-regulation of <i>HIF3A</i> partially antagonized the inhibitory effect of <i>miR-29b</i> over-expression on cell growth and migration. The enhancement of cell migration induced by <i>miR-29b</i> knockdown was attenuated by down-regulating <i>HIF3A</i>. These results imply that down-regulation of <i>miR-29b</i> may be related with the development of GDM partially via increasing the expression of <i>HIF3A</i>, which may provide a new insight for the mechanism of GDM.