Increased CAPG inhibits ferroptosis to drive tumor proliferation and sorafenib resistance in hepatocellular carcinoma via the WDR74-p53-SLC7A11 pathway

作者：Bing Quan, Fan Yao, Wenfeng Liu, Bei Tang, Miao Li, Shenxin Lu, Jinghuan Li, Rongxin Chen, Zhenggang Ren, Xin Yin · 发表于：International Journal of Biological Sciences · 年份：2025 · DOI：10.7150/ijbs.111419 · 被引用次数：4 · 研究领域：Ferroptosis and cancer prognosis、RNA modifications and cancer、Cholangiocarcinoma and Gallbladder Cancer Studies

assays, qPCR, and Western blot analyses were conducted to examine the relationship between CAPG expression and sorafenib treatment. Notably, CAPG was upregulated following sorafenib exposure and contributed to sorafenib resistance. RNA sequencing, ChIP sequencing, co-immunoprecipitation, and ubiquitination assays were further employed to elucidate the molecular mechanisms involving CAPG. Mechanistically, CAPG promoted gene expression by inducing WDR74 transcription, which modulated the interaction between p53 and MDM2, resulting in p53 degradation. Our findings demonstrate that CAPG drives tumor proliferation and sorafenib resistance by inhibiting ferroptosis, suggesting that CAPG may serve as a promising target in HCC.