CISD2 protects against Erastin induced hepatocellular carcinoma ferroptosis by upregulating FSP1

Abstract

Abstract Objectives CDGSH iron sulfur domain 2 (CISD2) is essential to maintain iron (Fe) and reactive oxygen species (ROS) homeostasis, and ferroptosis suppressor protein 1 (FSP1) can protect cells from ferroptosis by inhibiting lipid peroxidation. Here, we investigate the role and potential mechanism of CISD2 and FSP1 in ferroptosis of hepatocellular carcinoma (HCC). Methods Human HCC cells were exposed to ferroptosis inducer Erastin, and the expression changes of CISD2 and FSP1 during ferroptosis were detected. Subsequently, we investigated the effect of overexpression of CISD2 on ferroptosis and FSP1 expression in HCC cells. Finally, we also investigated the effect of overexpression of FSP1 on ferroptosis in HCC cells. Results Erastin induced ferroptosis in hepatoma cells, and HepG2 cells were sensitive to Erastin. In addition, it was found that the expression of CISD2 was significantly upregulated and the expression of FSP1 was significantly downregulated in Erastin treated HepG2 cells. Subsequently, CISD2 was found to be highly expressed in HCC tissues, and overexpression of CISD2 reversed ferroptosis induced by Erastin in HepG2 cells and upregulated the expression of FSP1. Meanwhile, FSP1 showed a low expression level in HCC tissues and cells, and overexpression of FSP1 could reverse the ferroptosis induced by Erastin in HepG2 cells. Conclusion CISD2 and FSP1 are involved in the ferroptosis process of HCC induced by Erastin. CISD2 protects against the ferroptosis of HCC induced by Erastin by upregulating the expression of FSP1.