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 antagomirs-a class of chemically modified anti-miRNA oligonucleotide-suppresses 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.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Ma L,Reinhardt F,Pan E,Soutschek J,Bhat B,Marcusson EG,Teruya-Feldstein J,Bell GW,Weinberg RAdoi
10.1038/nbt.1618subject
Has Abstractpub_date
2010-04-01 00:00:00pages
341-7issue
4eissn
1087-0156issn
1546-1696pii
nbt.1618journal_volume
28pub_type
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