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  • Exosomes derived from Fusobacterium nucleatum-infected colorectal cancer cells facilitate tumour metastasis by selectively carrying miR-1246/92b-3p/27a-3p and CXCL16

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Gut microbiota
Original research
Exosomes derived from Fusobacterium nucleatum-infected colorectal cancer cells facilitate tumour metastasis by selectively carrying miR-1246/92b-3p/27a-3p and CXCL16
  1. Songhe Guo1,
  2. Jun Chen1,
  3. Fangfang Chen1,
  4. Qiuyao Zeng2,3,
  5. Wan-Li Liu2,3,
  6. Ge Zhang1
  1. 1Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
  2. 2Department of Clinical Laboratory Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
  3. 3State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
  1. Correspondence to Dr Ge Zhang, Department of Microbial and Biochemical Pharmacy, Sun Yat-sen University, Guangzhou, China; zhangge{at}mail.sysu.edu.cn; Dr Wan-Li Liu, Department of Clinical Laboratory Medicine, Department of Clinical Laboratory Medicine, Sun Yat-sen University cancer center, Guangzhou, Guangdong, China; liuwl{at}sysucc.org.cn

Abstract

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

https://doi.org/10.1136/gutjnl-2020-321187

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    Footnotes

    • 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.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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