Cataracts are the leading cause of blindness in the world. Age is a major risk factor for cataracts, and with increasing aging, the burden of cataracts will grow, but the exact details of cataractogenesis remain unclear. A recent study showed that microRNA-34a (MIR34A) is involved in the development of cataracts, but the underlying pathogenesis remains obscure. Here, our results of microRNA target prediction showed that hexokinase 1 (HK1) is one of the genes targeted by MIR34A. Based on this finding, we focused on the function of MIR34A and HK1 in the progress of cataracts, whereby the human lens epithelial cell line SRA01/04 and mouse lens were treated with MIR34A mimics and HK1 siRNA. We found that HK1 mRNA is a direct target of MIR34A, whereby the high expression of MIR34A in the cataract lens suppresses the expression of HK1. In vitro, the upregulation of MIR34A together with the downregulation of HK1 inhibits the proliferation, induces the apoptosis of SRA01/04 cells, and accelerates the opacification of mouse lenses via the HK1/caspase 3 signaling pathway. In summary, our study demonstrates that MIR34A modulates lens epithelial cell (LEC) apoptosis and cataract development through the HK1/caspase 3 signaling pathway.
Keywords: HK1; MIR34A; apoptosis; caspase 3; cataract.