Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model Journal Article


Authors: Ma, L.; Reinhardt, F.; Pan, E.; Soutschek, J.; Bhat, B.; Marcusson, E. G.; Teruya-Feldstein, J.; Bell, G. W.; Weinberg, R. A.
Article Title: Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model
Abstract: MicroRNAs (miRNAs) are increasingly implicated in the regulation of metastasis. Despite their potential as targets for anti-metastatic therapy, miRNAs have only been silenced in normal tissues of rodents and nonhuman primates. Therefore, the development of effective approaches for sequence-specific inhibition of miRNAs in tumors remains a scientific and clinical challenge. Here we show that systemic treatment of tumor-bearing mice with miR-10b antagomirsa class of chemically modified anti-miRNA oligonucleotidesuppresses breast cancer metastasis. Both in vitro and in vivo, silencing of miR-10b with antagomirs significantly decreases miR-10b levels and increases the levels of a functionally important miR-10b target, Hoxd10. Administration of miR-10b antagomirs to mice bearing highly metastatic cells does not reduce primary mammary tumor growth but markedly suppresses formation of lung metastases in a sequence-specific manner. The miR-10b antagomir, which is well tolerated by normal animals, appears to be a promising candidate for the development of new anti-metastasis agents. © 2010 Nature America, Inc. All rights reserved.
Keywords: treatment outcome; unclassified drug; nonhuman; systemic therapy; mouse; animals; mice; mus; breast cancer; microrna; in vivo study; in vitro study; pathology; animalia; lung metastasis; tumors; breast tumor; neoplasm metastasis; gene silencing; rodentia; tumor growth; micrornas; disease models, animal; mammals; in-vitro; oligonucleotide; normal tissue; mammary neoplasms, experimental; antagomirs; chemically modified; mammary tumors; non-human primate; sequence-specific manner; bearings (structural); antagomir; microrna 10b; primates
Journal Title: Nature Biotechnology
Volume: 28
Issue: 4
ISSN: 1087-0156
Publisher: Nature Publishing Group  
Date Published: 2010-04-01
Start Page: 341
End Page: 347
Language: English
DOI: 10.1038/nbt.1618
PUBMED: 20351690
PROVIDER: scopus
PMCID: PMC2852471
DOI/URL:
Notes: --- - "Cited By (since 1996): 33" - "Export Date: 20 April 2011" - "CODEN: NABIF" - "Source: Scopus"
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  1. Julie T Feldstein
    297 Feldstein