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

• Published in: Nature communications Vol. 8; no. 1; p. 14448
• Main Authors: Teng, Yun, Ren, Yi, Hu, Xin, Mu, Jingyao, Samykutty, Abhilash, Zhuang, Xiaoying, Deng, Zhongbin, Kumar, Anil, Zhang, Lifeng, Merchant, Michael L., Yan, Jun, Miller, Donald M., Zhang, Huang-Ge
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17-02-2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/95; 631/67; 692/308; 96; 96/47; Animals; Base Sequence; Cell cycle; Cell Cycle Proteins - metabolism; Cell Line, Tumor; Colonic Neoplasms - blood; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Colorectal cancer; Disease Progression; Exosomes - metabolism; Female; Humanities and Social Sciences; Humans; Liver; Liver Neoplasms - pathology; Liver Neoplasms - secondary; Metastasis; Mice, Inbred BALB C; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; MicroRNAs - metabolism; Models, Biological; multidisciplinary; Neoplasm Invasiveness; Peptides; Proteins; RNA Transport; Science; Science (multidisciplinary); Tumor Microenvironment; Tumors; Vault Ribonucleoprotein Particles - metabolism; Louisville Kentucky; United States > US; Texas
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms14448

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.
Exosomes are involved in the development of metastasis but how their composition is regulated is not well known. Here the authors propose that major vault protein-dependent loading of miR-193a into exosomes could be a general mechanism by which cancer cells get rid of oncosuppressor miRNAs.