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

Front Endocrinol (Lausanne). 2020 Mar 31:11:169. doi: 10.3389/fendo.2020.00169. eCollection 2020.

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 miR-29b in the development of GDM. This study discovered that miR-29b expression was lower in placentas derived from patients with GDM than that in control placentas. MiR-29b over-expression inhibited cell growth and migration, and miR-29b knockdown promoted cell migration. Then we predicted and confirmed that HIF3A was a direct target of miR-29b with two specific binding sites at the recognition sequences of miR-29b in 3'-UTR of HIF3A mRNA, which was negatively correlated with miR-29b expression level. The up-regulation of HIF3A partially antagonized the inhibitory effect of miR-29b over-expression on cell growth and migration. The enhancement of cell migration induced by miR-29b knockdown was attenuated by down-regulating HIF3A. These results imply that down-regulation of miR-29b may be related with the development of GDM partially via increasing the expression of HIF3A, which may provide a new insight for the mechanism of GDM.

Keywords: HIF3A; gestational diabetes mellitus; human; miR-29b; placenta.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Apoptosis / genetics
  • Apoptosis Regulatory Proteins / genetics*
  • Case-Control Studies
  • Cell Adhesion / genetics
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Diabetes, Gestational / genetics*
  • Diabetes, Gestational / pathology
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation / genetics
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / physiology
  • Placenta / metabolism
  • Placenta / pathology
  • Placentation / genetics*
  • Pregnancy
  • Repressor Proteins / genetics*
  • Signal Transduction / genetics
  • Trophoblasts / metabolism
  • Trophoblasts / pathology
  • Trophoblasts / physiology*
  • Young Adult

Substances

  • Apoptosis Regulatory Proteins
  • HIF3A protein, human
  • MIRN29a microRNA, human
  • MicroRNAs
  • Repressor Proteins