miR-125b is methylated and functions as a tumor suppressor by regulating the ETS1 proto-oncogene in human invasive breast cancer

Cancer Res. 2011 May 15;71(10):3552-62. doi: 10.1158/0008-5472.CAN-10-2435. Epub 2011 Mar 28.


The microRNA miR-125b is dysregulated in various human cancers but its underlying mechanisms of action are poorly understood. Here, we report that miR-125b is downregulated in invasive breast cancers where it predicts poor patient survival. Hypermethylation of the miR-125b promoter partially accounted for reduction of miR-125b expression in human breast cancer. Ectopic restoration of miR-125b expression in breast cancer cells suppressed proliferation, induced G(1) cell-cycle arrest in vitro, and inhibited tumorigenesis in vivo. We identified the ETS1 gene as a novel direct target of miR-125b. siRNA-mediated ETS1 knockdown phenocopied the effect of miR-125b in breast cell lines and ETS1 overexpression in invasive breast cancer tissues also correlated with poor patient prognosis. Taken together, our findings point to an important role for miR-125b in the molecular etiology of invasive breast cancer, and they suggest miR-125b as a potential theranostic tool in this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA Methylation
  • Female
  • G1 Phase
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Prognosis
  • Proto-Oncogene Mas
  • Proto-Oncogene Protein c-ets-1 / metabolism*
  • Treatment Outcome


  • ETS1 protein, human
  • MAS1 protein, human
  • MIRN125 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Mas
  • Proto-Oncogene Protein c-ets-1