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

Nat Biotechnol. 2010 Apr;28(4):341-7. doi: 10.1038/nbt.1618. Epub 2010 Mar 28.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Female
  • Mammary Neoplasms, Experimental / genetics*
  • Mammary Neoplasms, Experimental / therapy*
  • Mice
  • MicroRNAs / administration & dosage*
  • MicroRNAs / genetics*
  • Neoplasm Metastasis / genetics*
  • Neoplasm Metastasis / therapy*
  • Treatment Outcome


  • MIRN10 microRNA, human
  • MicroRNAs