A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis

Cell. 2009 Jun 12;137(6):1032-46. doi: 10.1016/j.cell.2009.03.047.


MicroRNAs are well suited to regulate tumor metastasis because of their capacity to coordinately repress numerous target genes, thereby potentially enabling their intervention at multiple steps of the invasion-metastasis cascade. We identify a microRNA exemplifying these attributes, miR-31, whose expression correlates inversely with metastasis in human breast cancer patients. Overexpression of miR-31 in otherwise-aggressive breast tumor cells suppresses metastasis. We deploy a stable microRNA sponge strategy to inhibit miR-31 in vivo; this allows otherwise-nonaggressive breast cancer cells to metastasize. These phenotypes do not involve confounding influences on primary tumor development and are specifically attributable to miR-31-mediated inhibition of several steps of metastasis, including local invasion, extravasation or initial survival at a distant site, and metastatic colonization. Such pleiotropy is achieved via coordinate repression of a cohort of metastasis-promoting genes, including RhoA. Indeed, RhoA re-expression partially reverses miR-31-imposed metastasis suppression. These findings indicate that miR-31 uses multiple mechanisms to oppose metastasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Retracted Publication

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cytoskeletal Proteins / genetics
  • Frizzled Receptors / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Integrin alpha5 / genetics
  • Membrane Proteins / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Metastasis*
  • Receptors, G-Protein-Coupled / genetics
  • rhoA GTP-Binding Protein / genetics


  • Cytoskeletal Proteins
  • FZD3 protein, human
  • Frizzled Receptors
  • Integrin alpha5
  • MIRN31 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Mirn31 microRNA, mouse
  • Receptors, G-Protein-Coupled
  • radixin
  • rhoA GTP-Binding Protein