Epigenetic Regulation of G6PD Drives Metabolic Reprogramming in Intrahepatic Cholangiocarcinoma.

ABSTRACT: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy with poor prognosis and significant molecular heterogeneity. This study investigates the role of tumor-specific enhancers in metabolic reprogramming, focusing on glucose-6-phosphate dehydrogenase (G6PD) and the pentose phosphate pathway (PPP). Using native elongating transcript-cap analysis of gene expression and single-cell RNA sequencing, tumor-specific enhancers driving G6PD overexpression were identified in ICC tumor epithelial cells. Functional assays demonstrated that G6PD promotes tumor proliferation by enhancing PPP activity and maintaining redox homeostasis, which provides NADPH to counter oxidative stress. Enhancer knockdown disrupted G6PD expression and PPP activity, increasing reactive oxygen species levels

SUBMITTER: Nakano Y 

PROVIDER: S-EPMC12666459 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature