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Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model

MicroRNAs (miRNAs) are increasingly implicated in regulating metastasis. Despite progress in silencing miRNAs in normal tissues of rodents and non-human primates, the development of effective approaches for sequence-specific inhibition of miRNAs in fast-growing tumors remains a significant scientifi...

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Autores principales: Ma, Li, Reinhardt, Ferenc, Pan, Elizabeth, Soutschek, Jürgen, Bhat, Balkrishen, Marcusson, Eric, Teruya-Feldstein, Julie, Bell, George W., Weinberg, Robert A.
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2852471/
https://www.ncbi.nlm.nih.gov/pubmed/20351690
http://dx.doi.org/10.1038/nbt.1618
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author Ma, Li
Reinhardt, Ferenc
Pan, Elizabeth
Soutschek, Jürgen
Bhat, Balkrishen
Marcusson, Eric
Teruya-Feldstein, Julie
Bell, George W.
Weinberg, Robert A.
author_facet Ma, Li
Reinhardt, Ferenc
Pan, Elizabeth
Soutschek, Jürgen
Bhat, Balkrishen
Marcusson, Eric
Teruya-Feldstein, Julie
Bell, George W.
Weinberg, Robert A.
author_sort Ma, Li
collection PubMed
description MicroRNAs (miRNAs) are increasingly implicated in regulating metastasis. Despite progress in silencing miRNAs in normal tissues of rodents and non-human primates, the development of effective approaches for sequence-specific inhibition of miRNAs in fast-growing tumors remains a significant 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 oligonucleotides – suppresses breast cancer metastasis. Silencing of miR-10b both in vitro and in vivo with antagomirs significantly decreases miR-10b levels and increases 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 instead markedly suppresses formation of lung metastases. This metastasis-suppressing effect is sequence-specific. The miR-10b antagomir, which is well tolerated by normal animals, appears to be a promising candidate and a starting point for the development of new anti-metastasis agents.
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spelling pubmed-28524712010-10-01 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 Teruya-Feldstein, Julie Bell, George W. Weinberg, Robert A. Nat Biotechnol Article MicroRNAs (miRNAs) are increasingly implicated in regulating metastasis. Despite progress in silencing miRNAs in normal tissues of rodents and non-human primates, the development of effective approaches for sequence-specific inhibition of miRNAs in fast-growing tumors remains a significant 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 oligonucleotides – suppresses breast cancer metastasis. Silencing of miR-10b both in vitro and in vivo with antagomirs significantly decreases miR-10b levels and increases 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 instead markedly suppresses formation of lung metastases. This metastasis-suppressing effect is sequence-specific. The miR-10b antagomir, which is well tolerated by normal animals, appears to be a promising candidate and a starting point for the development of new anti-metastasis agents. 2010-03-28 2010-04 /pmc/articles/PMC2852471/ /pubmed/20351690 http://dx.doi.org/10.1038/nbt.1618 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Ma, Li
Reinhardt, Ferenc
Pan, Elizabeth
Soutschek, Jürgen
Bhat, Balkrishen
Marcusson, Eric
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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2852471/
https://www.ncbi.nlm.nih.gov/pubmed/20351690
http://dx.doi.org/10.1038/nbt.1618
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