Suppressing the OTUD7A/KDM5B/GABPA axis enhances the sensitivity of cisplatin through inducing ferroptosis in KRAS-mutant LUAD.

ABSTRACT: KRAS-mutant lung adenocarcinoma (LUAD), due to its evolution of more complex antioxidant metabolic mechanisms, exhibits poorer sensitivity to conventional platinum-based drugs compared to other types of LUAD. Ferroptosis, as a means of inducing cell death in cancer therapy, shows unique features and potential therapeutic effects compared to the conventional form of apoptosis, which is frequently obstructed by drug resistance. In human KRAS-mutant LUAD cell lines and mouse models, we found that the deubiquitinase OTU deubiquitinase 7A (OTUD7A) precisely regulates the lysine demethylase 5B (KDM5B). Inhibition of KDM5B expression increases the H4K20me3 level, which in turn downregulates the expression of transcription factor GABPA associated with mitochondrial function, ultimately promoting t

SUBMITTER: Si R 

PROVIDER: S-EPMC12848020 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature