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

ABSTRACTColorectal 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. nucleatumin the CRC metastasis. Our results showed that the abundance of F. nucleatumwas 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. nucleatumnot only increases CRC metastasis, but also participates in the reprograming of the tumor microenvironment. F. nucleatumpromoted 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. nucleatuminfection decreased the expression of miR-1322 by activating the NF-κB signaling pathway in CRC cells. In conclusion, F. nucleatumpromotes CRC metastasis through the miR-1322/CCL20 axis and M2 polarization.