MVP-mediated exosomal sorting of miR-193a promotes colon cancer progression

Yun Teng (), Yi Ren, Xin Hu, Jingyao Mu, Abhilash Samykutty, Xiaoying Zhuang, Zhongbin Deng, Anil Kumar, Lifeng Zhang, Michael L. Merchant, Jun Yan, Donald M. Miller and Huang-Ge Zhang ()
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Yun Teng: James Graham Brown Cancer Center, University of Louisville
Yi Ren: Huai'an First People's Hospital
Xin Hu: Program in Biostatistics, Bioinformatics and Systems Biology, The University of Texas Graduate School of Biomedical Sciences at Houston
Jingyao Mu: James Graham Brown Cancer Center, University of Louisville
Abhilash Samykutty: James Graham Brown Cancer Center, University of Louisville
Xiaoying Zhuang: James Graham Brown Cancer Center, University of Louisville
Zhongbin Deng: James Graham Brown Cancer Center, University of Louisville
Anil Kumar: James Graham Brown Cancer Center, University of Louisville
Lifeng Zhang: James Graham Brown Cancer Center, University of Louisville
Michael L. Merchant: Kidney Disease Program and Clinical Proteomics Center, University of Louisville
Jun Yan: James Graham Brown Cancer Center, University of Louisville
Donald M. Miller: James Graham Brown Cancer Center, University of Louisville
Huang-Ge Zhang: James Graham Brown Cancer Center, University of Louisville

Nature Communications, 2017, vol. 8, issue 1, 1-16

Abstract: Abstract Exosomes are emerging mediators of intercellular communication; whether the release of exosomes has an effect on the exosome donor cells in addition to the recipient cells has not been investigated to any extent. Here, we examine different exosomal miRNA expression profiles in primary mouse colon tumour, liver metastasis of colon cancer and naive colon tissues. In more advanced disease, higher levels of tumour suppressor miRNAs are encapsulated in the exosomes. miR-193a interacts with major vault protein (MVP). Knockout of MVP leads to miR-193a accumulation in the exosomal donor cells instead of exosomes, inhibiting tumour progression. Furthermore, miR-193a causes cell cycle G1 arrest and cell proliferation repression through targeting of Caprin1, which upregulates Ccnd2 and c-Myc. Human colon cancer patients with more advanced disease show higher levels of circulating exosomal miR-193a. In summary, our data demonstrate that MVP-mediated selective sorting of tumour suppressor miRNA into exosomes promotes tumour progression.

Date: 2017
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DOI: 10.1038/ncomms14448

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