ATF7IP inhibits Sorafenib-induced ferroptosis in hepatocellular carcinoma cells by inhibiting CYB5R2 transcription and stabilizing PARK7 protein.

ABSTRACT: Ferroptosis, an iron-dependent form of programmed cell death, arises from the accumulation of lipid peroxides at toxic levels. Sorafenib, a first-line treatment for advanced hepatocellular carcinoma, shows limited clinical efficacy due to drug resistance. However, the mechanisms underlying Sorafenib resistance, especially related to ferroptosis, remain poorly understood. In this study, we identify activating transcription factor 7-interacting protein (ATF7IP) as a key inhibitor of ferroptosis. ATF7IP depletion promotes Sorafenib-induced ferroptosis, resulting in decreased cell viability, reduced cellular glutathione (GSH) levels, increased lipid peroxidation, and altered mitochondrial crista structure. Notably, ATF7IP knockdown shows cooperative effects with Sorafenib in inhibiting hepatoc

SUBMITTER: Su Y 

PROVIDER: S-EPMC12314331 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature