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

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.