MicroRNA-34a suppresses human lens epithelial cell proliferation and migration via downregulation of c-Met

Clin Chim Acta. 2019 Aug:495:326-330. doi: 10.1016/j.cca.2019.04.060. Epub 2019 Apr 11.

Abstract

MicroRNAs (miRNAs) are endogenously expressed, non-coding, small RNAs which inhibit protein translation through binding to target mRNAs. Recent studies have demonstrated that miRNAs participate in the regulation of a variety of cell structures and functions including those for cell proliferation and migration. MicroRNA-34a (miR-34a), a potential effector of the p53 tumor suppressor gene, is extensively studied for its suppression of cell growth. In the present study, we investigated the function of miR-34a in human lens epithelial cells. Following confirming that miR-34a expression was increased in a P53 dependent manner in human lens epithelial cells after treatment with doxorubicin, we demonstrated that overexpression of miR-34a in the human lens epithelial cell line HLE B3 led to a significant decrease in cell proliferation and migration, with the use of MTS and transwell migration assays. Moreover, HGF enhanced the proliferation and migration of human lens epithelial cells. miR-34a was found to downregulate the expression of c-Met protein by Western blotting. Furthermore, overexpression of miR-34a downregulated the levels of phosphorylated Akt, phosphorylated ERK1/2 and other cell cycle regulators. miR-34a expression was significantly reduced in posterior capsule opacification (PCO) clinical samples. These results demonstrate that miR-34a may act as a suppressor in PCO by regulating human lens epithelial cell proliferation and migration through downregulation of c-Met.

Keywords: C-met; Migration; Posterior capsule opacification; Proliferation; miR-34a.

MeSH terms

  • Capsule Opacification / metabolism
  • Capsule Opacification / prevention & control
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Down-Regulation
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Humans
  • Lens, Crystalline / cytology*
  • MicroRNAs / metabolism
  • MicroRNAs / pharmacology
  • MicroRNAs / physiology*
  • Phosphorylation
  • Proto-Oncogene Proteins c-met / metabolism*
  • Tumor Suppressor Protein p53

Substances

  • MIRN34 microRNA, human
  • MicroRNAs
  • Tumor Suppressor Protein p53
  • MET protein, human
  • Proto-Oncogene Proteins c-met