Fusobacterium nucleatum promotes colorectal cancer metastasis by excretion of miR-122-5p from cells via exosomes

Mengjiao Zhang; Yifeng Wang; Longchen Yu; Yanli Zhang; Yanlei Wang; Ziqi Shang; Yiwei Xin; Xinyang Li; Nannan Ning; Yi Zhang; Xin Zhang

doi:10.1016/j.isci.2023.107686

Fusobacterium nucleatum promotes colorectal cancer metastasis by excretion of miR-122-5p from cells via exosomes

iScience. 2023 Aug 19;26(9):107686. doi: 10.1016/j.isci.2023.107686. eCollection 2023 Sep 15.

Authors

Mengjiao Zhang^{1

2}, Yifeng Wang^{1

2}, Longchen Yu^{1

2}, Yanli Zhang³, Yanlei Wang⁴, Ziqi Shang^{1

2}, Yiwei Xin^{1

2}, Xinyang Li^{1

2}, Nannan Ning^{1

2}, Yi Zhang^{1

2}, Xin Zhang^{1

2}

Affiliations

¹ Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan 250012, China.
² Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, China.
³ Department of Clinical Laboratory, Shandong Provincial Third Hospital, Jinan 250031, China.
⁴ Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, China.

Abstract

Fusobacterium nucleatum (Fn) infection and microRNAs (miRNAs) are closely associated with colorectal cancer (CRC) development, but the mechanism by which Fn regulates tumor-suppressive miRNAs via exosomes and facilitates CRC metastasis remains unclear. Here, we identified that Fn infection significantly increased exosomal miR-122-5p levels in the serum of CRC patients and CRC cell culture supernatants through two miRNA panels of high-throughput sequencing and RT-qPCR analysis. In Fn-infected patients, the serum exosomal levels of miR-122-5p were negatively associated with their expression levels of tissues. Downregulated miR-122-5p was demonstrated to enhance the migration, invasion, and metastasis abilities of CRC cells in vivo and in vitro. Secretion of miR-122-5p into exosomes is mediated by hnRNPA2B1. Mechanistically, Fn activated the TGF-β1/Smads signaling pathway to promote EMT by regulation of the miR-122-5p/FUT8 axis. In conclusion, Fn infection may stimulate CRC cells to excrete exosome-wrapped miR-122-5p, and activate the FUT8/TGF-β1/Smads axis to promote metastasis.

Keywords: Bacteriology; Cell biology; Microbiology.