Suppressive role of miR-502-5p in breast cancer via downregulation of TRAF2

Oncol Rep. 2014 May;31(5):2085-92. doi: 10.3892/or.2014.3105. Epub 2014 Mar 21.


TRAF2 promotes cancer cell survival, proliferation and metastasis through the NF-κB pathway by directly interacting with various TNF recepors. However, the molecular mechanism of TRAF2 dysregulation in breast cancer remains to be elucidated. In the present study, miR-502-5p was predicted as a potential regulator of TRAF2. miR-502-5p was significantly downregulated in breast cancer tissues when compared to the level in paired normal breast tissues. The breast cancer cell lines including MCF-7 and MDA-MB-231 expressed a lower level of miR-502-5p when compared to the level in the non-malignant breast epithelial cell line MCF-10A. In vitro, miR-502-5p enhanced early apoptosis and inhibited proliferation of breast cancer cells. Luciferase reporter assay results showed that miR-502-5p could bind to the 3'-untranslated region of the TRAF2 gene, thus, exerting an inhibitory effect on TRAF2. Furthermore, silencing of TRAF2 exhibited effects similar to those of exogenous miR‑502-5p, while overexpression of TRAF2 partially abrogated miR-502-5p-mediated suppression in breast cancer cells. In conclusion, miR-502-5p may act as a tumor-suppressor gene by targeting oncogenic TRAF2 in breast cancer and, therefore, may be a potential diagnostic and anticancer therapeutic marker for breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Apoptosis / genetics
  • Biomarkers, Tumor / genetics
  • Breast / pathology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • HEK293 Cells
  • Humans
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • NF-kappa B
  • Neoplasm Metastasis / genetics
  • Protein Binding / genetics
  • RNA Interference
  • RNA, Small Interfering
  • TNF Receptor-Associated Factor 2 / biosynthesis
  • TNF Receptor-Associated Factor 2 / genetics*


  • 3' Untranslated Regions
  • Biomarkers, Tumor
  • MIRN502 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • RNA, Small Interfering
  • TNF Receptor-Associated Factor 2