MicroRNA-29b regulates TGF-β1-mediated epithelial-mesenchymal transition of retinal pigment epithelial cells by targeting AKT2

Exp Cell Res. 2016 Jul 15;345(2):115-24. doi: 10.1016/j.yexcr.2014.09.026. Epub 2014 Sep 28.

Abstract

The role of microRNA (miRNA) in proliferative vitreoretinopathy (PVR) progression has not been studied extensively, especially in retinal pigment epithelial-mesenchymal transition (EMT) which is the main reason for formation of PVR. In this study, we first investigated the miRNA expression profile in transforming growth factor beta 1 (TGF-β1) mediated EMT of ARPE-19 cells. Among the five changed miRNAs, miR-29b showed the most significant downregulation. Enhanced expression of miR-29b could reverse TGF-β1 induced EMT through targeting Akt2. Akt2 downregulation could inhibit TGF-β1-induced EMT. Furthermore, inhibition of miR-29b in ARPE-19 cells directly triggered EMT process, which characterized by the phenotypic transition and the upregulation of α-smooth muscle actin (α-SMA) and downregulation of E-cadherin and zona occludin-1 (ZO-1) with increased cell migration. Akt2-shRNA also inhibited miR-29 inhibitor-induced EMT process. These data indicate that miR-29b plays an important role in TGF-β1-mediated EMT in ARPE-19 cells by targeting Akt2.

Keywords: Akt2; EMT; MicroRNA-29b; Retinal pigment epithelial cells.

MeSH terms

  • Base Sequence
  • Down-Regulation / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Epithelial-Mesenchymal Transition / genetics
  • HEK293 Cells
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Retinal Pigment Epithelium / drug effects
  • Retinal Pigment Epithelium / metabolism
  • Retinal Pigment Epithelium / pathology*
  • Transforming Growth Factor beta1 / pharmacology*

Substances

  • MIRN29a microRNA, human
  • MicroRNAs
  • Transforming Growth Factor beta1
  • AKT2 protein, human
  • Proto-Oncogene Proteins c-akt