Research Papers:
Selective extracellular vesicle exclusion of miR-142-3p by oral cancer cells promotes both internal and extracellular malignant phenotypes
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Abstract
Christopher T.D. Dickman1, James Lawson1, James Jabalee1, Sara A. MacLellan1, Nancy E. LePard1, Kevin L. Bennewith1,2, Cathie Garnis1,3
1Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada
2Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
3Division of Otolaryngology, Department of Surgery, University of British Columbia, Vancouver, BC, Canada
Correspondence to:
Cathie Garnis, email: [email protected]
Keywords: MiRNA, exosome, TGFBR1, oral squamous cell carcinoma, oral dysplasia
Received: September 01, 2016 Accepted: January 16, 2017 Published: January 27, 2017
ABSTRACT
Packaging of small molecular factors, including miRNAs, into small extracellular vesicles (SEVs) may contribute to malignant phenotypes and facilitate communication between cancer cells and tumor stroma. The process by which some miRNAs are enclosed in SEVs is selective rather than indiscriminate, with selection in part governed by specific miRNA sequences. Herein, we describe the selective packaging and removal via SEVs of four miRNAs (miR-142-3p, miR-150-5p, miR-451a, and miR-223-3p) in a panel of oral dysplasia and oral squamous cell carcinoma cell lines. Inhibition of exosome export protein Rab27A increased intracellular concentration of these miRNA candidates and prevented their exclusion via SEVs. Increased intracellular miR-142-3p specifically was found to target TGFBR1, causing a decrease in TGFBR1 expression in donor cells and a reduction of malignant features such as growth and colony formation. Conversely, increased excretion of miR-142-3p via donor cell SEVs and uptake by recipient endothelial cells was found to reduce TGFBR1 activity and cause tumor-promoting changes in these cells in vitro and in vivo.
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