Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model
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Author(s)
Ma, Li
Reinhardt, Ferenc
Pan, Elizabeth
Soutschek, Jürgen
Bhat, Balkrishen
Marcusson, Eric G
Teruya-Feldstein, Julie
Bell, George W
Weinberg, Robert A
Date Issued
March 2010
Journal
Nature Biotechnology
Publisher
Nature Publishing Group
Citation
Ma, Li et al. “Therapeutic Silencing of miR-10b Inhibits Metastasis in a Mouse Mammary Tumor Model.” Nature Biotechnology 28, 4 (March 2010): 341–347 © 2010 Nature America, Inc
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Ludwig Center for Molecular Oncology (Massachusetts Institute of Technology)
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DOI of Published Version
https://doi.org/10.1038/nbt.1618
