Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model
Author(s)Ma, Li; Reinhardt, Ferenc; Pan, Elizabeth; Soutschek, Jürgen; Bhat, Balkrishen; Marcusson, Eric G; Teruya-Feldstein, Julie; Bell, George W; Weinberg, Robert A; ... Show more Show less
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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.
DepartmentLudwig Center for Molecular Oncology; Massachusetts Institute of Technology. Department of Biology
Nature Publishing Group
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
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