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 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.
Ma
Li
L
Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Reinhardt
Ferenc
F
Pan
Elizabeth
E
Soutschek
Jürgen
J
Bhat
Balkrishen
B
Marcusson
Eric G
EG
Teruya-Feldstein
Julie
J
Bell
George W
GW
Weinberg
Robert A
RA
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000628:therapy*; D051379:Mice; D035683:MicroRNAs / Q000008:administration & dosage* / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000628:therapy*; D016896:Treatment Outcome
C547183:MIRN10 microRNA, human; D035683:MicroRNAs