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MVP-mediated exosomal sorting of miR-193a promotes colon cancer progression
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.
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“MVP knockout colon carcinoma cells led to an accumulation of cytosolic miR-193a and a decrease of miR-193a in cell-derived exosomes, while no change in miR-126a was observed [71].”
From Differential RNA packaging into small extracellular vesicles by neurons and astrocytes (2021) · cites this paper as [71]
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Metadata
- Authors
- Teng, Y., Ren, Y., Hu, X., Mu, J., Samykutty, A., Zhuang, X., Deng, Z., Kumar, A., Zhang, L., Merchant, M. L., Yan, J., Miller, D. M., & Zhang, H.-G.
- Venue
- Nature Communications
- Published
- 2017-02-17
- Volume
- 8
- Issue
- 1
- ISSN
- 2041-1723
- Cited by
- 408
- References
- 3
- Language
- en
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