MicroRNA-362-5p promotes the proliferation and inhibits apoptosis of trophoblast cells via targeting glutathione-disulfide reductase

Bioengineered. 2021 Dec;12(1):2410-2419. doi: 10.1080/21655979.2021.1933678.

Abstract

Gestational diabetes mellitus (GDM), a common complication of pregnancy, harms the health of pregnant women and fetuses. MicroRNAs (miRNAs) dysregulation in placenta is involved in GDM. Herein, we explored the roles of miR-362-5p in GDM. After high glucose (HG) treated HTR-8/SVneo cells, CCK-8 and flow cytometry were conducted to assess the capability of the proliferation and apoptosis, respectively. The data demonstrated that HG inhibited proliferation and induced apoptosis of HTR-8/SVneo cells. MiR-362-5p level was reduced in HG-treated cells and placenta tissues of GDM patients, measured by qPCR. Overexpressed miR-362-5p accelerated the proliferation and restrained apoptosis of HG-treated cells. Furthermore, glutathione-disulfide reductase (GSR) was verified as a target of miR-362-5p, through TargetScan database and dual-luciferase reporter assay. GSR was upregulated in GDM placenta tissues and was negatively regulated by miR-362-5p. Enforced GSR level abolished the effects of miR-362-5p overexpression on the proliferation and apoptosis of HTR-8/SVneo cells. Furthermore, miR-362-5p increased p-PI3K, p-AKT and bcl-2, while reduced bax and cleaved caspase3, which were abolished by GSR. In conclusion, miR-362-5p promoted cell proliferation and inhibited apoptosis via targeting GSR and activating PI3K/AKT pathway. The findings mentioned above suggested that miR-362-5p might be a therapy target of GDM.

Keywords: GSR; Gestational diabetes mellitus; apoptosis; miR-362-5p; proliferation.

MeSH terms

  • Adult
  • Apoptosis* / genetics
  • Base Sequence
  • Caspase 3 / metabolism
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Diabetes, Gestational / genetics
  • Diabetes, Gestational / pathology
  • Down-Regulation / drug effects
  • Female
  • Glucose / toxicity
  • Glutathione Reductase / metabolism*
  • HEK293 Cells
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Pregnancy
  • Proto-Oncogene Proteins c-akt / metabolism
  • Trophoblasts / cytology*
  • Trophoblasts / drug effects
  • Trophoblasts / metabolism*
  • bcl-2-Associated X Protein / metabolism

Substances

  • MIRN362 microRNA, human
  • MicroRNAs
  • bcl-2-Associated X Protein
  • Glutathione Reductase
  • Proto-Oncogene Proteins c-akt
  • Caspase 3
  • Glucose