G6PD inhibits ferroptosis in hepatocellular carcinoma by targeting cytochrome P450 oxidoreductase.

Ferroptosis is an important cell necrosis and has been a focus in cancer related research.Increcsing studies have focused on the phenotype and function of ferroptosis in tumorigenesis, but the underlying mechanism remains poorly understood. Here, we used bioinformatics approaches to identify differentially expressed genes associated with HCC and ferroptosis. We found that G6PD (glucose-6-phosphate dehydrogenase) was highly expressed in HCC and was associated with poor prognosis. G6PD promoted the proliferation, migration and invasion, as well as inhibited ferroptosis in HCC cells. Pathway and functional enrichment analyses revealed that G6PD was related to the P450 metabolic pathway. POR (cytochrome P450 oxidoreductase) was downregulated in HCC and was significantly correlated with the prognosis. G6PD inhibited ferroptosis inin HCC cells through POR. Knockdown of G6PD reduced the tumor volume and tumor weight in vivo. Our study demonstrated that G6PD deficiency suppresses cell growth, metastasis, and tumorigenesis via upregulating POR, suggesting that G6PD may be used as a biomarker for the treatment of HCC in the future.