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" |
