1. Cancer Exosomes Perform Cell-Independent MicroRNA Biogenesis and Promote Tumorigenesis
- Author
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Lev T. Perelman, Raghu Kalluri, Edward Vitkin, Cristina Ivan, Joyce T. O’Connell, Noritoshi Kato, Le Qiu, Anthony Lucci, Alberto Villanueva, George A. Calin, Sonia A. Melo, Carlos A. Melo, Hikaru Sugimoto, and August Vidal
- Subjects
0303 health sciences ,Cancer Research ,biology ,Cancer ,Cell Biology ,Argonaute ,medicine.disease_cause ,medicine.disease ,Microvesicles ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,microRNA ,Cancer cell ,Immunology ,biology.protein ,medicine ,Cancer research ,Gene silencing ,Carcinogenesis ,030304 developmental biology ,Dicer - Abstract
SummaryExosomes 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.
- Published
- 2014