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.
- colorectal cancer
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GZ and W-LL contributed equally.
Correction notice This article has been corrected since it published Onine First. The first affiliations has been updated and a sentence within the 'Identification of exosome proteins and functional categorisation in Fn-infected CRC cells' paragraph has been amended.
Contributors SG, WLL, QZ and GZ: acquisition of data, analysis and interpretation of data, statistical analysis and drafting of the manuscript. SG, JC and FC: technical and material support. WLL and GZ: study concept and design, analysis and interpretation of data, drafting of the manuscript, obtained funding and study supervision. All authors read and approved the final manuscript.
Funding This work was supported by the National Natural Science Foundation of China (No. 81673005; No. 81972289)
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. ManuscriptFigureSupplementary File.
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