MicroRNA-15a modulates lens epithelial cells apoptosis and proliferation through targeting B-cell lymphoma-2 and E2F transcription factor 3 in age-related cataracts

Abstract

Age-related cataract remains a serious problem in the aged over the world. MicroRNAs are abnormally expressed in various diseases including age-related cataract. MicroRNA-15a (MicroRNA-15a) has been involved in various diseases and plays crucial roles in many cellular processes. However, the mechanism of microRNA-15a in the genesis of cataract remains barely known. We therefore aimed to investigate the role of microRNA-15a in the cataract. Herein, human lens epithelial B3 cells, HLE-B3 cells were treated with 200 μmol/l H2O2 for 24 h. H2O2 was utilized in our study to induce HLE-B3 cells injury. We observed that cell apoptosis was induced by the treatment of H2O2 and meanwhile, cell proliferation was repressed by 200 μmol/l H2O2. Then, it was found that microRNA-15a was significantly increased with the H2O2 exposure in vitro. Importantly, B-cell lymphoma-2 (BCL2) and E2F transcription factor 3 (E2F3) exert crucial roles in cell apoptosis and cell proliferation. We found that BCL2 and E2F3 were greatly reduced by 200 μmol/l H2O2 in human lens epithelial cells. In addition, microRNA-15a overexpression induced cell apoptosis and repressed cell proliferation through suppressing BCL2 and E2F3. Subsequently, BCL2 and E2F3 were predicted as a direct target of microRNA-15a. The direct correlation between microRNA-15a and BCL2/E2F3 was confirmed by dual luciferase reporter assay. In conclusion, we demonstrated that microRNA-15a triggered apoptosis and repressed the proliferation of HLE-B3 cells by modulating BCL2 and E2F3.