Fusobacterium nucleatum promotes colorectal cancer metastasis through miR-1322/CCL20 axis and M2 polarization

被引:193
作者
Xu, Chaochao [1 ,3 ]
Fan, Lina [2 ,4 ]
Lin, Yifeng [2 ,4 ]
Shen, Weiyi [1 ,3 ]
Qi, Yadong [1 ,3 ]
Zhang, Ying [1 ,3 ]
Chen, Zhehang [1 ,3 ]
Wang, Lan [1 ,3 ]
Long, Yanqin [1 ]
Hou, Tongyao [1 ,3 ]
Si, Jianmin [1 ,3 ,4 ]
Chen, Shujie [1 ,3 ,4 ]
机构
[1] Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Gastroenterol, 3 Qingchun East Rd, Hangzhou 310003, Peoples R China
[2] Zhejiang Univ, Dept Gastroenterol, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China
[3] Zhejiang Univ, Inst Gastroenterol, Hangzhou, Peoples R China
[4] Zhejiang Univ, Canc Ctr, Hangzhou, Zhejiang, Peoples R China
关键词
Colorectal cancer; Fusobacterium nucleatum; macrophage infiltration; CCL20; metastasis; KAPPA-B; CHEMOKINES; CELLS; CCL20; SUPPORT;
D O I
10.1080/19490976.2021.1980347
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Colorectal cancer (CRC) is one of the most common malignant tumors and is associated with Fusobacterium nucleatum (F. nucleatum, Fn) infection. In this study, we explored the role of F. nucleatum in the CRC metastasis. Our results showed that the abundance of F. nucleatum was enriched in the feces and tumors of patients with CRC and tended to increase in stage IV compared to stage I in patients with metastatic CRC. Tumor-derived CCL20 activated by F. nucleatum not only increases CRC metastasis, but also participates in the reprograming of the tumor microenvironment. F. nucleatum promoted macrophage infiltration through CCL20 activation and simultaneously induced M2 macrophage polarization, enhancing the metastasis of CRC. In addition, we identified using database prediction and luciferase activity hat miR-1322, a candidate regulatory micro-RNA, could bind to CCL20 directly. F. nucleatum infection decreased the expression of miR-1322 by activating the NF-kappa B signaling pathway in CRC cells. In conclusion, F. nucleatum promotes CRC metastasis through the miR-1322/CCL20 axis and M2 polarization.
引用
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页数:17
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