Local microRNA delivery targets Palladin and prevents metastatic breast cancer

Avital Gilam, João Conde, Daphna Weissglas-Volkov, Nuria Oliva, Eitan Friedman, Natalie Artzi () and Noam Shomron ()
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Avital Gilam: Sackler Faculty of Medicine, Tel-Aviv University
João Conde: Massachusetts Institute of Technology, Institute for Medical Engineering and Science
Daphna Weissglas-Volkov: Sackler Faculty of Medicine, Tel-Aviv University
Nuria Oliva: Massachusetts Institute of Technology, Institute for Medical Engineering and Science
Eitan Friedman: The Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, Chaim Sheba Medical Center Tel-Hashomer
Natalie Artzi: Massachusetts Institute of Technology, Institute for Medical Engineering and Science
Noam Shomron: Sackler Faculty of Medicine, Tel-Aviv University

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms12868

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