MicroRNA-204-5p Regulates Epithelial-to-Mesenchymal Transition during Human Posterior Capsule Opacification by Targeting SMAD4

Abstract

PURPOSE: To investigate the role of microRNA (miRNA) in regulating epithelial-to-mesenchymal transition (EMT) during human posterior capsule opacification (PCO). METHODS: A miRCURY LNA microRNA array was used to evaluate the miRNA profiles of human PCO tissues and normal attached lens epithelial cells (LECs). An in vitro human donor capsular bag model was used to investigate the role of miRNAs in the EMT during PCO. The expression of SMAD4, phospho-SMAD2/3, and a panel of EMT markers was detected by Western blot and quantitative RT-PCR. RESULTS: The results of miRNA profiling in human PCO tissues and normal attached LECs demonstrated that, among other miRNAs, miR-204-5p expression was down-regulated. Using bioinformatics, we identified SMAD4, one of the mediators of TGF-β/SMAD signaling, as a predicted target of miR-204-5p. Overexpression of miR-204-5p in primary LECs increased E-cadherin expression and decreased the expression of vimentin and alpha smooth muscle actin. Furthermore, miR-204-5p overexpression enhanced the repression of TGF-β2-induced EMT in the presence of SMAD4 small interfering RNA. CONCLUSIONS: Our data provide firm evidence of a role for miR-204-5p in the direct regulation of EMT through its targeting of SMAD4 and, consequently, TGF-β signaling. Because of its ability to repress the EMT, miR-204-5p may be a novel target for PCO therapeutic intervention.