Egr-1 regulates irradiation-induced autophagy through Atg4B to promote radioresistance in hepatocellular carcinoma cells.

Although hepatocellular carcinoma (HCC) is usually response to radiation therapy, radioresistance is still the major obstacle that limits the efficacy of radiotherapy for HCC patients. Therefore, further investigation of underlying mechanisms in radioresistant HCC cells is warranted. In this study, we determined the effect of early growth response factor (Egr-1) on irradiation-induced autophagy and radioresistance in HCC cell lines SMMC-7721 and HepG2. We showed that autophagy-related gene 4B (Atg4B) is induced by Egr-1 upon ionizing radiation (IR) in HCC cells. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) revealed that Egr-1 binds to the Atg4B promoter to upregulate its expression in HCC cells. Suppression of Egr-1 function by dominant-negative Egr-1 dampens IR-induced autophagy, cell migration, and increases cell sensitivity to radiotherapy. Together, these results suggest that Egr-1 contributes to HCC radioresistance through directly upregulating target gene Atg4B, which may serve as a protective mechanism by preferential activation of the autophagy.