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MicroRNA-31 induced by Fusobacterium nucleatum infection promotes colorectal cancer tumorigenesis

作者:Bin Tang, Xiaoxue Lu, Yanan Tong, Yuyang Feng, Yilan Mao, Guodong Dun, Jing Li, Qiao-Lin Xu, Jie Tang, Tao Zhang, Ling Deng, Xiaoyi He, Yuanzhi Lan, Hua-xing Luo, Linghai Zeng, Yuanyuan Xiang, Qian Li, Dong-zhu Zeng, Xuhu Mao · 发表于:iScience · 年份:2023 · DOI:10.1016/j.isci.2023.106770 · 被引用次数:31 · 研究领域:Autophagy in Disease and Therapy、Cancer-related molecular mechanisms research、Mycobacterium research and diagnosis

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.