miR-892b Silencing Activates NF-κB and Promotes Aggressiveness in Breast Cancer

Cancer Res. 2016 Mar 1;76(5):1101-11. doi: 10.1158/0008-5472.CAN-15-1770. Epub 2016 Jan 8.


The strength and duration of NF-κB signaling is tightly controlled at multiple levels under physiologic conditions, but the mechanism underlying constitutive activation of the NF-κB pathway in cancer remains unclear. In this study, we investigated miRNA-mediated regulation of the NF-κB cascade in breast cancer. We report that miR-892b expression was significantly downregulated in human breast cancer specimens and correlated with poor patient survival. Overexpression of miR-892b in breast cancer cells significantly decreased tumor growth, metastatic capacity, and the ability to induce angiogenesis, whereas miR-892b depletion enhanced these properties, in vitro and in vivo. Furthermore, we demonstrate that miR-892b attenuated NF-κB signaling by directly targeting and suppressing multiple mediators of NF-κB, including TRAF2, TAK1, and TAB3, and thus, miR-892b silencing in breast cancer cells sustains NF-κB activity. Moreover, miR-892b downregulation was attributed to aberrant hypermethylation of its promoter. Taken together, our results provide insight into a new mechanism by which NF-κB signaling becomes constitutively activated in breast cancer and suggest a tumor-suppressive role for miR-829b, prompting further investigation into miRNA mimics for cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • DNA Methylation
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / physiology*
  • NF-kappa B / physiology*
  • Polyubiquitin / metabolism
  • Promoter Regions, Genetic
  • Signal Transduction / physiology


  • MIRN892 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • Polyubiquitin