MicroRNA-30c-5p ameliorates hypoxia-reoxygenation-induced tubular epithelial cell injury via HIF1α stabilization by targeting SOCS3

Abstract

The cellular hypoxia-reoxygenation (H/R) model is an ideal method to study ischemia-reperfusion injury, which is associated with high mortality. The role of microRNA-30c-5p (miR-30c-5p) in the H/R epithelial cell model remains unknown. In the current study, we observed a significant reduction in apoptosis when miR-30c-5p was up-regulated. We also found decreased levels of C-caspase-3 (C-CASP3) and Bcl-2-associated X (BAX) proteins and increased levels of B-cell lymphoma-2 (BCL2). Epidermal growth factor receptor (EGFR) showed similar results. Down-regulating miR-30c-5p increased the levels of apoptosis and C-CASP3 and BAX expression; additionally, cell proliferation was inhibited. Hypoxia-inducible factor 1α (HIF1α) protein expression levels were up-regulated in response to up-regulation of miR-30c-5p expression. The anti-apoptotic and proliferative effects of miR-30c-5p decreased significantly after the HIF1α protein levels were knocked down. Using a luciferase reporter assay, we confirmed that miR-30c-5p targets suppressor of cytokine signaling-3 (SOCS3). HIF1α levels increased when SOCS3 was blocked. Our data show that SOCS3 expression enhances apoptosis in the H/R model. In conclusion, up-regulating miR-30c-5p protects cells from H/R -induced apoptosis and induces cell proliferation; furthermore, HIF1α markedly contributes to this protective effect. MiR-30c-5p stabilizes HIF1α expression by targeting SOCS3 to achieve anti-apoptotic and proliferative effects.