Oncosuppressive role of p53-induced miR-205 in triple negative breast cancer

Mol Oncol. 2012 Aug;6(4):458-72. doi: 10.1016/j.molonc.2012.03.003. Epub 2012 Apr 19.


An increasing body of evidence highlights an intriguing interaction between microRNAs and transcriptional factors involved in determining cell fate, including the well known "genome guardian" p53. Here we show that miR-205, oncosuppressive microRNA lost in breast cancer, is directly transactivated by oncosuppressor p53. Moreover, evaluating miR-205 expression in a panel of cell lines belonging to the highly aggressive triple negative breast cancer (TNBC) subtype, which still lacks an effective targeted therapy and characterized by an extremely undifferentiated and mesenchymal phenotype, we demonstrated that this microRNA is critically down-expressed compared to a normal-like cell line. Re-expression of miR-205 where absent strongly reduces cell proliferation, cell cycle progression and clonogenic potential in vitro, and inhibits tumor growth in vivo, and this tumor suppressor activity is at least partially exerted through targeting of E2F1, master regulator of cell cycle progression, and LAMC1, component of extracellular matrix involved in cell adhesion, proliferation and migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Cellular Senescence / genetics
  • Down-Regulation / genetics
  • E2F1 Transcription Factor / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Laminin / metabolism
  • Mice
  • Mice, SCID
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Sequence Data
  • Protein Binding
  • Response Elements / genetics
  • Transcription, Genetic
  • Tumor Suppressor Protein p53 / metabolism*
  • Xenograft Model Antitumor Assays


  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Laminin
  • MIRN205 microRNA, human
  • MicroRNAs
  • Tumor Suppressor Protein p53
  • laminin gamma 1