AP2a-Mediated Upregulation of miR-125a-5p Ameliorates Radiation-Induced Oxidative Stress Injury via BRD4/Nrf2/HO-1 Signaling.

Abstract

Radiation therapy is widely used to restrain tumor progression, but it is always accompanied by damage to healthy tissues. We aimed to probe the impact and mechanism of activator protein 2a (AP2a) and miR-125a-5p in radiation-induced oxidative stress injury. Human umbilical vein endothelial cells (HUVECs) were treated with X rays to induce radiation injury in vitro. Cell viability was measured using MTT assays. Flow cytometry assay was employed to detect the apoptosis rate. Oxidative stress markers were evaluated by detection kits. Gene or protein levels were determined by RT-qPCR or Western blotting. Validation of the interaction of miR-125a-5p with BRD4 and AP2a was conducted by dual luciferase assay or ChIP. MiR-125a-5p and AP2a were decreased in irradiated HUVECs, whereas BRD4 was increased. MiR-125a-5p overexpression or BRD4 silencing alleviated the cell viability decline, apoptosis, and oxidative stress injury caused by radiation treatment. MiR-125a-5p repressed the BRD4 level. The protective effects of miR-125a-5p overexpression in the radiation-induced oxidative injury were impeded by BRD4 overexpression. Moreover, AP2a bound to the promoter of miR-125a-5p. MiR-125a-5p inhibition reversed the effects of AP2a overexpression on radiational oxidative injury by modulating Nrf2/HO-1 signaling. AP2a transcriptionally activated miR-125a-5p ameliorated oxidative stress injury of HUVECs caused by radiation through Nrf2/HO-1 signaling.