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Local microRNA delivery targets Palladin and prevents metastatic breast cancer

Author

Listed:
  • Avital Gilam

    (Sackler Faculty of Medicine, Tel-Aviv University)

  • João Conde

    (Massachusetts Institute of Technology, Institute for Medical Engineering and Science
    School of Engineering and Materials Science, Queen Mary University of London)

  • 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
    Broad Institute of MIT and Harvard
    Brigham and Women’s Hospital, Harvard Medical School)

  • Noam Shomron

    (Sackler Faculty of Medicine, Tel-Aviv University)

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.

Suggested Citation

  • Avital Gilam & João Conde & Daphna Weissglas-Volkov & Nuria Oliva & Eitan Friedman & Natalie Artzi & Noam Shomron, 2016. "Local microRNA delivery targets Palladin and prevents metastatic breast cancer," Nature Communications, Nature, vol. 7(1), pages 1-14, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12868
    DOI: 10.1038/ncomms12868
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