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

Gut Microbes. 2021 Jan-Dec;13(1):1980347. doi: 10.1080/19490976.2021.1980347.

Abstract

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-κB signaling pathway in CRC cells. In conclusion, F. nucleatum promotes CRC metastasis through the miR-1322/CCL20 axis and M2 polarization.

Keywords: CCL20; Colorectal cancer; Fusobacterium nucleatum; macrophage infiltration; metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement
  • Cell Polarity
  • Chemokine CCL20 / genetics
  • Chemokine CCL20 / metabolism*
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / microbiology*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / physiopathology
  • Feces / microbiology
  • Female
  • Fusobacterium Infections / metabolism
  • Fusobacterium Infections / microbiology
  • Fusobacterium Infections / pathology
  • Fusobacterium Infections / physiopathology
  • Fusobacterium nucleatum / physiology*
  • Gastrointestinal Microbiome
  • Humans
  • Macrophages / cytology*
  • Macrophages / metabolism
  • Male
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Neoplasm Metastasis

Substances

  • CCL20 protein, human
  • Chemokine CCL20
  • MIRN1322 microRNA, human
  • MicroRNAs
  • NF-kappa B

Grants and funding

This work was supported by the Zhejiang Provincial Medical and Health Science and Technology Project [2019KY412, 2019RC043, 2021RC070]; Natural Science Foundation of Zhejiang province under grant [LY20H030009, Q22H169506]; Zhejiang Province Public Welfare Technology Research Project [LGD20H030002, LGD21H160002].