G6PD inhibits ferroptosis in hepatocellular carcinoma by targeting cytochrome P450 oxidoreductase

• Published in: Cellular signalling Vol. 87; p. 110098
• Main Authors: Cao, Fei, Luo, Anguo, Yang, Chaowen
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.11.2021
• Subjects: Carcinoma, Hepatocellular - pathology; Cell Line, Tumor; Cell migration and invasion; Cell Movement; Cell Proliferation; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; Ferroptosis; G6PD; Gene Expression Regulation, Neoplastic; Glucosephosphate Dehydrogenase - genetics; Glucosephosphate Dehydrogenase - metabolism; Glucosephosphate Dehydrogenase Deficiency - genetics; HCC; Humans; Liver Neoplasms - pathology; POR; Cell proliferation; Ferroptosis; HCC; G6PD; POR; Cell migration and invasion
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2021.110098

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. •G6PD was overexpressed in HCC and associated with poor survival.•G6PD was the only gene in the intersection of four different datasets.•G6PD positively regulated cell viability and metastasis in HCC cells.•G6PD suppressed ferroptosis through the cytochrome P450 metabolic pathway in HCC cells.•G6PD and its associated genes were mainly enriched for a function in lipid metabolism, especially the cytochrome P450 metabolic pathway.•POR expression was positively related with survival rates, in which high POR expression indicated a better prognosis.