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

By Li Ma, Ferenc Reinhardt, Elizabeth Pan, J. Soutschek, B. Bhat, E. Marcusson, J. Teruya-Feldstein, George W. Bell, R. Weinberg. Nature Biotechnology, 2010

782 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a5b5bda5b8313d0afdae45c0bf45d72eb04fb710

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

In Molecular Biology

Citations in the corpus

Tumor Metastasis: Molecular Insights and Evolving Paradigms (2011, background): “Unfortunately, however, the rationale behind many targeted agents that were designed to impair carcinoma metastasis, such as MMP inhibitors, the Axl kinase inhibitor R428, miR-10b antagonists, and the fascin inhibitor Migrastatin, is incompatible with these clinical observations, as these compounds ”
Long intergenic non-coding RNAs – New links in cancer progression (2011, background): “In another study (34), intravenous administration of the antagomir did not reduce primary mammary tumor growth, but it did strikingly”
Non-coding RNAs in human disease (2011, background): “The efficacy of ASOs has been demonstrated in some cases; for example, in a mouse mammary tumour model, the intravenous injection of antagomirs targeting miR-10b prevents the onset of metastasis, suppressing dissemination to the lung”
MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy (2011, positive): “A similar scenario was observed for miR-10b, which is upregulated in — and seems to be restricted to — metastatic lesions (as discussed below in the 'miRNA-based therapeutics' section”
TGF-β-Mediated Epithelial-Mesenchymal Transition and Cancer Metastasis (2019, background): “In contrast, silencing of miR-10b markedly suppressed the formation of lung metastases by inhibiting its target gene HOXD10 in a mouse mammary tumor model [110].”
MicroRNA sponges: progress and possibilities. (2010, background): “A similar approach was taken to show that miR-10b (Ma et al. 2010a) and miR-9 (Ma et al.”
The ins and outs of the epithelial to mesenchymal transition in health and disease. (2011, background): “Nevertheless, some hope comes from several studies showing that systemic administration of microRNAs or aptamer-siRNA chimeras inhibit tumorigenesis and metastasis in mouse models (Dassie et al. 2009, Kota et al. 2009, Ma et al. 2010).”
Targeting MicroRNAs in Cancer: Rationale, Strategies and Challenges (2010, positive): “Furthermore, a recent study reported that silencing mir-10b inhibits metastasis in a mouse breast tumour model, thereby highlighting the therapeutic potential of targeting metastasis-associated miRNA”