MicroRNA-31 induced by Fusobacterium nucleatum infection promotes colorectal cancer tumorigenesis
Bin Tang,
Xiaoxue Lu,
Yanan Tong,
Yuyang Feng,
Yilan Mao,
Guodong Dun,
Jing Li,
Qiaolin Xu,
Jie Tang,
Tao Zhang,
Ling Deng,
Xiaoyi He,
Yuanzhi Lan,
Huaxing Luo,
Linghai Zeng,
Yuanyuan Xiang,
Qian Li,
Dongzhu Zeng,
Xuhu Mao
Affiliations
Bin Tang
Department of Clinical Laboratory, Chongqing University Jiangjin Hospital, School of Medicine, Chongqing University, Jiangjin, Chongqing 402260, China
Xiaoxue Lu
Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), Chongqing 400038, China
Yanan Tong
Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), Chongqing 400038, China
Yuyang Feng
Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), Chongqing 400038, China
Yilan Mao
Class of 2021 undergraduate, Nursing College of Chongqing Medical University, Chongqing 400016, China
Guodong Dun
Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), Chongqing 400038, China
Jing Li
Department of General Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China
Qiaolin Xu
Department of General Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China
Jie Tang
Department of General Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China
Tao Zhang
Department of General Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China
Ling Deng
Department of General Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China
Xiaoyi He
Department of General Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China
Yuanzhi Lan
Department of General Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China
Huaxing Luo
Department of General Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China
Linghai Zeng
Department of General Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China
Yuanyuan Xiang
Department of General Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China
Qian Li
Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), Chongqing 400038, China; Corresponding author
Dongzhu Zeng
Department of General Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China; Corresponding author
Xuhu Mao
Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), Chongqing 400038, China; Corresponding author
Summary: Persistent Fusobacterium nucleatum infection is associated with the development of human colorectal cancer (CRC) and promotes tumorigenicity, but the underlying mechanisms remain unclear. Here, we reported that F. nucleatum promoted the tumorigenicity of CRC, which was associated with F. nucleatum-induced microRNA-31 (miR-31) expression in CRC tissues and cells. F. nucleatum infection inhibited autophagic flux by miR-31 through inhibiting syntaxin-12 (STX12) and was associated with the increased intracellular survival of F. nucleatum. Overexpression of miR-31 in CRC cells promoted their tumorigenicity by targeting eukaryotic initiation factor 4F-binding protein 1/2 (eIF4EBP1/2), whereas miR-31 knockout mice were resistant to the formation of colorectal tumors. In conclusion, F. nucleatum, miR-31, and STX12 form a closed loop in the autophagy pathway, and continuous F. nucleatum-induced miR-31 expression promotes the tumorigenicity of CRC cells by targeting eIF4EBP1/2. These findings reveal miR-31 as a potential diagnostic biomarker and therapeutic target in CRC patients with F. nucleatum infection.
