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

Cell | Jun 12, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19524507

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.

Pubmed ID: 19524507 RIS Download

Mesh terms: Animals | Breast Neoplasms | Cell Line, Tumor | Cytoskeletal Proteins | Frizzled Receptors | Gene Expression Regulation, Neoplastic | Humans | Integrin alpha5 | Membrane Proteins | MicroRNAs | Neoplasm Metastasis | Receptors, G-Protein-Coupled | rhoA GTP-Binding Protein

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Associated grants

  • Agency: NCI NIH HHS, Id: P01 CA080111
  • Agency: NCI NIH HHS, Id: P01 CA080111
  • Agency: NCI NIH HHS, Id: P01 CA080111-01
  • Agency: NCI NIH HHS, Id: R01 CA078461
  • Agency: NCI NIH HHS, Id: R01 CA078461
  • Agency: NCI NIH HHS, Id: R01 CA078461-01A1

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