MicroRNA-486 down-regulates p53 expression in the diabetic retinopathy

Objective: To investigate the role of miR-486 in the pathogenesis of diabetic retinopathy and the possible mechanism involved in it. Methods: Electroretinography was used to measure the function of STZ (streptozotocin)induced diabetic mice. MiRNA expression changes in the retinas of STZ-induced diabetic mice were identified by miRNA-specific microarray and further confirmed by quantitative RT-PCR (qRT-PCR). The potential downstream targets of identified miRNAs were predicted by bioinformatic analysis and confirmed by dual luciferase assay. The downstream targets were identified by molecular analysis. Results: MiR-486 was up-regulated significantly in the STZ-induced diabetic mice retina. Sequence analysis and luciferase assay identified p53 as a downstream target gene regulated by miR-486. Besides, in a human Muller cell line (MIO-M1), transfection of a miR-486 mimic downregulated p53 expression. Conversely, transfection of MIO-M1 with a miR-486 inhibitor resulted in up-regulated p53. Furthermore, over-expression of recombinant p53 attenuated oxidative stress marker, nitration of cellular proteins, and ameliorated apoptosis induced by 4-hydroxynonenal (4-HNE), an oxidative stressor. Similarly, transfection of a miR-486 inhibitor decreased, whereas transfection of miR-486 mimic increased the number of apoptotic cells following 4-HNE treatment. Conclusion: These results suggested that miR-486-regulated p53 potentially has a protective role in diabetic retinopathy.