HBx Inhibits the Ferroptosis in HBV‐Associated Hepatocellular Carcinoma Through Upregulation of SIRT1

Hepatocellular carcinoma (HCC) seriously threatens the health of people, and the effective strategies against HCC remain limited. Meanwhile, HBx is reported to play a key role in HBV-caused HCC. However, the detailed mechanism underlying the impact of HBx in HCC is unexplored. To study the function of HBx in HCC, CCK8 was applied for testing cell viability, and the proliferation of HCC cells was assessed by colony formation assay. The mitochondrial morphology and structure were observed using transmission electron microscope (TEM). Cell invasion and migration were assessed using Transwell. The live/dead cells were analyzed with calcein AM/PI kit, and ROS, MDA, and GSH levels were examined by commercial kits. The results indicated HBx and SIRT1 were upregulated in HBV-associated HCC. Upregulation of HBx promoted the invasion, proliferation, and migration of HCC cells, and it could inhibit Bax level and upregulate Bcl-2 expression. Erastin obviously induced ferroptosis of HCC cells as well as decreased the volume of mitochondria, while overexpression of HBx reversed this phenomenon. HBx upregulation significantly abolished Erastin-induced HCC cells ferroptosis. SIRT1 silencing caused ferroptosis of HCC cells. HBx attenuated ferroptosis in HCC through upregulation of SIRT1. To sum up, HBx inhibits the ferroptosis in HCC cells through upregulation of SIRT1. Thus, our research supplied a novel strategy in alleviating the tumorigenesis of HCC.