DDX5 deficiency drives non-canonical NF-κB activation and NRF2 expression, influencing sorafenib response and hepatocellular carcinoma progression.

ABSTRACT: In advanced hepatocellular carcinoma (HCC), RNA helicase DDX5 regulates the Wnt/β-catenin-ferroptosis axis, influencing the efficacy of the multi-tyrosine kinase inhibitor (mTKI) sorafenib. DDX5 inhibits Wnt/β-catenin signaling, preventing sorafenib-induced ferroptosis escape. Sorafenib/mTKIs reduce DDX5 expression, correlating with poor patient survival post-sorafenib treatment. Notably, DDX5-knockout in HCC cells activates Wnt/β-catenin signaling persistently. Herein, we investigate the mechanistic impact of Wnt/β-catenin activation resulting from DDX5 downregulation in the progression and treatment of HCC. RNAseq analyses identified shared genes repressed by DDX5 and upregulated by sorafenib, including Wnt signaling genes, NF-κB-inducing kinase (NIK) essential for non-canonical NF-κB (p

SUBMITTER: Li Z 

PROVIDER: S-EPMC11315975 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature