Journal
GUT
Volume 70, Issue 8, Pages 1507-1519Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/gutjnl-2020-321187
Keywords
colorectal cancer
Categories
Funding
- National Natural Science Foundation of China [81673005, 81972289]
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This study demonstrates that exosomes from Fn-infected cells deliver miR-1246/92b-3p/27a-3p and CXCL16/RhoA/IL-8 to non-infected cells, increasing cell migration ability in vitro and promoting tumor metastasis in vivo. Additionally, circulating exosomal levels of miR-1246/92b-3p/27a-3p and CXCL16 are closely associated with Fn abundance and tumor stage in colorectal cancer patients.
Objective Exosomes released from tumour cells are packed with unique RNA and protein cargo, and they are emerging as an important mediator in the communication network that promotes tumour progression. The facultative intracellular bacterium Fusobacterium nucleatum (Fn) is an important colorectal cancer (CRC)-associated bacterium. To date, the function of exosomes from Fn-infected CRC cells has not been explored. Design Exosomes were isolated by sequential differential centrifugation and verified by transmission electron microscopy, NanoSight analysis and Western blotting. Given that exosomes have been shown to transport miRNAs and proteins to alter cellular functions, we performed miRNA sequencing and proteome analysis of exosomes from Fn-infected and non-infected cells. The biological role and mechanism of exosomes from Fn-infected cells in CRC tumour growth and liver metastasis were determined in vitro and in vivo. Results We demonstrated that exosomes delivered miR-1246/92b-3p/27a-3p and CXCL16/RhoA/IL-8 from Fn-infected cells into non-infected cells to increase cell migration ability in vitro and promote tumour metastasis in vivo. Finally, both circulating exosomal miR-1246/92b-3p/27a-3p and CXCL16 levels were closely associated with Fn abundance and tumour stage in patients with CRC. Conclusion This study suggests that Fn infection may stimulate tumour cells to generate miR-1246/92b-3p/27a-3p-rich and CXCL16/RhoA/IL-8 exosomes that are delivered to uninfected cells to promote prometastatic behaviours.
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