Local microRNA delivery targets Palladin and prevents metastatic breast cancer
Name
Local microRNA.pdf
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4.85 MB
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Author(s)
Gilam, Avital
Weissglas-Volkov, Daphna
Friedman, Eitan
Shomron, Noam
Osorio De Castro Conde, Joao
Artzi, Natalie
Oliva, Nuria
Date Issued
September 2016
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Gilam, Avital et al. “Local microRNA Delivery Targets Palladin and Prevents Metastatic Breast Cancer.” Nature Communications 7 (2016): 12868.
Version
Final published version
Abstract
Metastasis is the primary cause for mortality in breast cancer. MicroRNAs, gene expression master regulators, constitute an attractive candidate to control metastasis. Here we show that breast cancer metastasis can be prevented by miR-96 or miR-182 treatment, and decipher the mechanism of action. We found that miR-96/miR-182 downregulate Palladin protein levels, thereby reducing breast cancer cell migration and invasion. A common SNP, rs1071738, at the miR-96/miR-182-binding site within the Palladin 3′-UTR abolishes miRNA:mRNA binding, thus diminishing Palladin regulation by these miRNAs. Regulation is successfully restored by applying complimentary miRNAs. A hydrogel-embedded, gold-nanoparticle-based delivery vehicle provides efficient local, selective, and sustained release of miR-96/miR-182, markedly suppressing metastasis in a breast cancer mouse model. Combined delivery of the miRNAs with a chemotherapy drug, cisplatin, enables significant primary tumour shrinkage and metastasis prevention. Our data corroborate the role of miRNAs in metastasis, and suggest miR-96/miR-182 delivery as a potential anti-metastatic drug.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Terms of Use
Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1038/ncomms12868
