ISG15 Enhances the Activity of γ-Glutamate Cysteine Ligase to Suppress Apoptosis in High Fat Diet-Promoted Hepatocellular Carcinoma.

ABSTRACT: Obesity is a leading risk factor for development of hepatocellular carcinoma (HCC). High-fat intake produces cytotoxic effects in liver cells, such as excessive reactive oxygen species (ROS) accumulation and apoptosis. How HCC cells regulate ROS level and escape the cytotoxic effects of high fat diet (HFD) stress remains unclear. Herein, this work reports a critical anti-ROS/apoptotic role of the ubiquitin-like protein interferon stimulated gene 15 (ISG15) in HFD-promoted HCC. In mouse models and clinical HCC samples, upregulation of ISG15 is associated with hepatic steatosis. Notably, upregulated ISG15 elevates cellular glutathione levels, which subsequently reduces ROS accumulation and confers resistance to apoptosis in HCC cells. In diethylnitrosamine-induced HCC mouse model, HFD-feedin

SUBMITTER: Liu X 

PROVIDER: S-EPMC12097128 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature