TY - JOUR
T1 - Local microRNA delivery targets Palladin and prevents metastatic breast cancer
AU - Gilam, Avital
AU - Conde, João
AU - Weissglas-Volkov, Daphna
AU - Oliva, Nuria
AU - Friedman, Eitan
AU - Artzi, Natalie
AU - Shomron, Noam
N1 - Funding Information: Israel Science Foundation (No. 1852/16)
PY - 2016/9/19
Y1 - 2016/9/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84988350368&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/ncomms12868
DO - https://doi.org/10.1038/ncomms12868
M3 - مقالة
SN - 2041-1723
VL - 7
JO - Nature Communications
JF - Nature Communications
M1 - 12868
ER -
