Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model
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...
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| Format: | Article |
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Nature Publishing Group
2018
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| Online Access: | http://hdl.handle.net/1721.1/116969 https://orcid.org/0000-0002-0895-3557 |
| _version_ | 1826206928720625664 |
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| author | Ma, Li Reinhardt, Ferenc Pan, Elizabeth Soutschek, Jürgen Bhat, Balkrishen Marcusson, Eric G Teruya-Feldstein, Julie Bell, George W Weinberg, Robert A |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Ma, Li Reinhardt, Ferenc Pan, Elizabeth Soutschek, Jürgen Bhat, Balkrishen Marcusson, Eric G Teruya-Feldstein, Julie Bell, George W Weinberg, Robert A |
| author_sort | Ma, Li |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:40:47Z |
| format | Article |
| id | mit-1721.1/116969 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T13:40:47Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1169692022-10-01T16:28:59Z Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model Ma, Li Reinhardt, Ferenc Pan, Elizabeth Soutschek, Jürgen Bhat, Balkrishen Marcusson, Eric G Teruya-Feldstein, Julie Bell, George W Weinberg, Robert A Massachusetts Institute of Technology. Department of Biology Ludwig Center for Molecular Oncology (Massachusetts Institute of Technology) Ma, Li Weinberg, Robert A 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. 2018-07-13T13:31:36Z 2018-07-13T13:31:36Z 2010-03 2010-01 2018-07-12T18:13:00Z Article http://purl.org/eprint/type/JournalArticle 1087-0156 1546-1696 http://hdl.handle.net/1721.1/116969 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 https://orcid.org/0000-0002-0895-3557 http://dx.doi.org/10.1038/nbt.1618 Nature Biotechnology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | Ma, Li Reinhardt, Ferenc Pan, Elizabeth Soutschek, Jürgen Bhat, Balkrishen Marcusson, Eric G Teruya-Feldstein, Julie Bell, George W Weinberg, Robert A Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model |
| title | Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model |
| title_full | Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model |
| title_fullStr | Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model |
| title_full_unstemmed | Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model |
| title_short | Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model |
| title_sort | therapeutic silencing of mir 10b inhibits metastasis in a mouse mammary tumor model |
| url | http://hdl.handle.net/1721.1/116969 https://orcid.org/0000-0002-0895-3557 |
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