IDI1 inhibits the cGAS-Sting signaling pathway in hepatocellular carcinoma
Lin Fu,
Hui Ding,
Yangqiu Bai,
Lina Cheng,
Shanshan Hu,
Qiongya Guo
Affiliations
Lin Fu
Corresponding author.; Department of Gastroenterology, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, 7th Weiwu Road, Zhengzhou, 450000, Henan, China
Hui Ding
Department of Gastroenterology, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, 7th Weiwu Road, Zhengzhou, 450000, Henan, China
Yangqiu Bai
Corresponding author. Henan Provincial People's Hospital, 7th Weiwu Road, Zhengzhou, 450000, Henan, China.; Department of Gastroenterology, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, 7th Weiwu Road, Zhengzhou, 450000, Henan, China
Lina Cheng
Department of Gastroenterology, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, 7th Weiwu Road, Zhengzhou, 450000, Henan, China
Shanshan Hu
Department of Gastroenterology, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, 7th Weiwu Road, Zhengzhou, 450000, Henan, China
Qiongya Guo
Department of Gastroenterology, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, 7th Weiwu Road, Zhengzhou, 450000, Henan, China
Metabolic reprogramming is one of the prominent features that distinguishes tumor cells from normal cells. The role of metabolic abnormalities in regulating innate immunity is poorly understood. In this study, we found that IDI1 is significantly upregulated in liver cancer. IDI1 has no significant effect on the growth or invasion of liver cancer cells but significantly promotes liver cancer development in mice. Through molecular mechanism studies, we found that IDI1 interacts with the important regulator of innate immunity cGAS and recruits the E3 ligase TRIM41 to promote cGAS ubiquitination and degradation, inhibiting the cGAS-Sting signaling pathway. IDI1 inhibits the phosphorylation of TBK1 and the downstream factor IRF3 as well as the expression of CCL5 and CXCL10. In summary, this study revealed the important role of the metabolic enzyme IDI1 in the regulation of innate immunity, suggesting that it may be a potential target for liver cancer treatment.
