miR-7 Reduces High Glucose Induced-damage Via HoxB3 and PI3K/AKT/mTOR Signaling Pathways in Retinal Pigment Epithelial Cells

Curr Mol Med. 2020;20(5):372-378. doi: 10.2174/1566524019666191023151137.

Abstract

Background: Diabetic retinopathy (DR) is a common complication of diabetes. This study investigated the effect of miR-7 in the regulation of cell proliferation via the HoxB3 gene and PI3K/AKT/mTOR signaling pathways in DR.

Methods: Human retinal pigment epithelial cell line (ARPE-19) cultured in normal medium (Control) and high glucose medium (25mM glucose, HG) was transfected with mimics NC (HG+ mimics NC), miR-7 mimics (HG+miR-7 mimics), inhibitor NC (HG+ inhibitor NC), and miR-inhibitor (HG+miR-7 inhibitor). The cells were assayed for viability, apoptosis, and expression of genes.

Results: HG reduced cell viability and increased apoptosis. However, miR-7 mimics reduced the apoptosis. PCR results showed that miR-7 was significantly upregulated after transfection with miR-7 mimics. The expression of Hoxb3, mTOR, p-PI3K, and p- AKT was significantly downregulated at mRNA and protein levels after miR-7 mimics transfection, while no difference was observed for PI3K and AKT expression.

Conclusion: Our findings demonstrate that miR-7 regulates the growth of retinal epithelial cells through various pathways and is a potential therapeutic target for the prevention and treatment of diabetic retinopathy.

Keywords: DR; HoxB3; PI3K/AKT/mTOR signaling; celll proliferation; miR-7; retinopathy..

MeSH terms

  • Apoptosis / physiology
  • Cell Line
  • Cell Proliferation / physiology
  • Cell Survival / physiology
  • Down-Regulation / physiology
  • Epithelial Cells / metabolism*
  • Glucose / metabolism*
  • Homeodomain Proteins / metabolism*
  • Humans
  • MicroRNAs / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Retinal Pigment Epithelium / metabolism*
  • Retinal Pigments / metabolism*
  • Signal Transduction / physiology*
  • TOR Serine-Threonine Kinases / metabolism
  • Up-Regulation / physiology

Substances

  • Homeodomain Proteins
  • HoxB3 protein, human
  • MIRN7 microRNA, human
  • MicroRNAs
  • Retinal Pigments
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Glucose