MicroRNA-335 inhibits tumor reinitiation and is silenced through genetic and epigenetic mechanisms in human breast cancer

Genes Dev. 2011 Feb 1;25(3):226-31. doi: 10.1101/gad.1974211.


Post-transcriptional regulators have emerged as robust effectors of metastasis and display deregulated expression through unknown mechanisms. Here, we reveal that the human microRNA-335 locus undergoes genetic deletion and epigenetic promoter hypermethylation in every metastatic derivative obtained from independent patients' malignant cell populations. Genetic deletion of miR-335 is a common event in human breast cancer, is enriched for in breast cancer metastases, and also correlates with ovarian cancer recurrence. We furthermore identify miR-335 as a robust inhibitor of tumor reinitiation. We thus implicate the miR-335 locus on 7q32.2 as the first selective metastasis suppressor and tumor initiation suppressor locus in human breast cancer.

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.

MeSH terms

  • Breast Neoplasms / physiopathology*
  • Cell Line, Tumor
  • DNA Methylation
  • Epigenesis, Genetic*
  • Female
  • Gene Deletion
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / physiopathology*
  • Promoter Regions, Genetic / genetics
  • RNA Interference*


  • MIRN335 microRNA, human
  • MicroRNAs

Associated data

  • GEO/GSE9586