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Local microRNA delivery targets Palladin and prevents metastatic breast cancer.

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Gilam A,Conde J,Weissglas-Volkov D,Oliva N,Friedman E,Artzi N,Shomron N

doi

10.1038/ncomms12868

subject

Has Abstract

pub_date

2016-09-19 00:00:00

pages

12868

issn

2041-1723

pii

ncomms12868

journal_volume

7

pub_type

杂志文章

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