Cancer Cell
Volume 26, Issue 5, 10 November 2014, Pages 707-721
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Article
Cancer Exosomes Perform Cell-Independent MicroRNA Biogenesis and Promote Tumorigenesis

https://doi.org/10.1016/j.ccell.2014.09.005Get rights and content
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Highlights

  • Cancer exosomes use Dicer, TRBP, and AGO2 to process pre-miRNAs to generate miRNAs

  • CD43 mediates accumulation of Dicer specifically in cancer exosomes

  • Cancer exosomes alter the transcriptome of target cells in a Dicer-dependent manner

  • Breast cancer serum exosomes process pre-miRNAs into miRNAs inducing tumor formation

Summary

Exosomes are secreted by all cell types and contain proteins and nucleic acids. Here, we report that breast cancer associated exosomes contain microRNAs (miRNAs) associated with the RISC-Loading Complex (RLC) and display cell-independent capacity to process precursor microRNAs (pre-miRNAs) into mature miRNAs. Pre-miRNAs, along with Dicer, AGO2, and TRBP, are present in exosomes of cancer cells. CD43 mediates the accumulation of Dicer specifically in cancer exosomes. Cancer exosomes mediate an efficient and rapid silencing of mRNAs to reprogram the target cell transcriptome. Exosomes derived from cells and sera of patients with breast cancer instigate nontumorigenic epithelial cells to form tumors in a Dicer-dependent manner. These findings offer opportunities for the development of exosomes based biomarkers and therapies.

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