CircEZH2 promotes gallbladder cancer progression and lipid metabolism reprogramming through the miR-556-5p/SCD1 axis
Huanjun Tong,
Xiaopeng Yu,
Difan Zhou,
Zhihong Shen,
Jialu Chen,
Yu Si,
Lulu Zhang,
Baochun Lu,
Jianhua Yu,
Shouhua Wang,
Zhaohui Tang
Affiliations
Huanjun Tong
Department of Hepatobiliary Surgery, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, Zhejiang, China; Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Department of Blood Transfusion, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Shaoxing Key Laboratory of Minimally Invasive Abdominal Surgery and Precise Treatment of Tumour, Shaoxing, Zhejiang, China
Xiaopeng Yu
Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Department of Blood Transfusion, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Shanghai Clinical Research Ward (SCRW), Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
Difan Zhou
Department of Hepatobiliary Surgery, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, Zhejiang, China; Shaoxing Key Laboratory of Minimally Invasive Abdominal Surgery and Precise Treatment of Tumour, Shaoxing, Zhejiang, China
Zhihong Shen
Department of Hepatobiliary Surgery, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, Zhejiang, China; Shaoxing Key Laboratory of Minimally Invasive Abdominal Surgery and Precise Treatment of Tumour, Shaoxing, Zhejiang, China
Jialu Chen
Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Department of Blood Transfusion, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Yu Si
Department of Blood Transfusion, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Lulu Zhang
Department of Hepatobiliary Surgery, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, Zhejiang, China
Baochun Lu
Department of Hepatobiliary Surgery, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, Zhejiang, China; Shaoxing Key Laboratory of Minimally Invasive Abdominal Surgery and Precise Treatment of Tumour, Shaoxing, Zhejiang, China
Jianhua Yu
Department of Hepatobiliary Surgery, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, Zhejiang, China; Shaoxing Key Laboratory of Minimally Invasive Abdominal Surgery and Precise Treatment of Tumour, Shaoxing, Zhejiang, China
Shouhua Wang
Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Corresponding author
Zhaohui Tang
Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Department of Blood Transfusion, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Corresponding author
Summary: Gallbladder cancer (GBC) is characterized by a high degree of malignancy and a poor prognosis. This study revealed that circEZH2 was frequently upregulated in GBC tissues and correlated with advanced tumor-node-metastasis (TNM) stage in GBC patients. In vitro and in vivo experiments confirmed that circEZH2 promoted the proliferation and inhibited the ferroptosis of GBC. Besides, this study discovered that circEZH2 regulated lipid metabolism reprogramming in GBC cells. Mechanistically, circEZH2 promotes SCD1 expression by sponging miR-556-5p in GBC cells. In addition, IGF2BP2 enhances the stability of circEZH2 in an m6A-dependent manner, while circEZH2 suppresses the ubiquitination and degradation of IGF2BP2 by binding to IGF2BP2. Taken together, our findings indicated that circEZH2, upregulated via a positive feedback loop between circEZH2 and IGF2BP2, promotes GBC progression and lipid metabolism reprogramming through the miR-556-5p/SCD1 axis in GBC. circEZH2 may serve as a potential therapeutic target for GBC.
