NSDHL promotes the degradation of sting in cholangiocarcinoma
Weihua Yu,
Jionghuang Chen,
Yifan Tong,
Linghua Zhu,
Yuezheng Deng,
Junju He,
Chenxi Zhong,
Xiujun Cai
Affiliations
Weihua Yu
Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China
Jionghuang Chen
Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China
Yifan Tong
Liver Regeneration and Metabolism Study Group, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China
Linghua Zhu
Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China
Yuezheng Deng
Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China
Junju He
Department of Oncology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, 430060, China; Corresponding author. Renmin Hospital of Wuhan University, China
Chenxi Zhong
Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China; Corresponding author. Shanghai Chest Hosipital, China
Xiujun Cai
Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China; Corresponding author.
Metabolic enzymes play significant roles in tumor growth via nonmetabolic biological processes. However, more research is needed to understand their roles in immune modulation. This study revealed that 3-hydroxysteroid dehydrogenase (NSDHL) expression was elevated in cholangiocarcinoma. In vitro experiments demonstrated that NSDHL had no effect on the growth or invasion of cholangiocarcinoma cells in an artificial laboratory environment. However, NSDHL overexpression strongly enhanced the promotion of AKT/YAP-driven cholangiocarcinoma. NSDHL bound to STING and facilitated its degradation via ubiquitination. This inhibited the cyclic-GMP-AMP-synthase-STING signaling pathway and reduced the synthesis of IFNβ. A study revealed an inverse relationship between the expression of NSDHL and the infiltration of NK cells, activated CD4+ T cells, and neutrophils in individuals who were diagnosed with cholangiocarcinoma. This study elucidates the role of NSDHL, in addition to its established metabolic functions, NSDHL regulates the cyclic-GMP-AMP-synthase signaling pathway. By exploring this interplay, this research enriches our understanding of the functions of NSDHL in terms of cellular dynamics, offering novel insights into the modulation of crucial biological pathways.
