MVP-mediated selective sorting of tumour suppressor miRNA into exosomes promotes tumour progression

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, researchers from the University of Louisville 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, these data demonstrate that MVP-mediated selective sorting of tumour suppressor miRNA into exosomes promotes tumour progression.

 miRNA profile from exosomes is different from their donor cells

(a) Comparative analysis of the miRNome in exosomes and exosome donor tissues using a microarray. miRNAs from exosomes and exosome donor tissues, including primary colon cancer (top panel) and liver metastasis (middle panel), were quantitatively analysed and expressed as a ratio of miRNAs from exosome donor tissues/exosomes. The similarity of each individual miRNA distribution in primary colon cancer and liver metastasis was analysed by overlaying each and are shown in yellow (bottom panel). Expression of miR-193a (b), miR-18a (c) and miR-21 (d) in the exosomes and exosome donor tissues, including primary colon cancer and liver metastasis of colon cancer, were assessed by qPCR. *P<0.05 (two-tailed t-test). Data are representative of three independent experiments (error bars, s.e.m.).