MicroRNA-196a post-transcriptionally upregulates the UBE2C proto-oncogene and promotes cell proliferation in breast cancer

Oncol Rep. 2015 Aug;34(2):877-83. doi: 10.3892/or.2015.4049. Epub 2015 Jun 11.


Accumulating evidence has shown that miR-196a plays an important role in tumorigenesis and tumor progression in various types of cancer. miRNA profiling studies have suggested that miR-196a is highly overexpressed in breast cancer. However, the functional mechanism of miR-196a in breast cancer remains unclear. In the present study, we first showed that the expression of miR-196a was significantly upregulated in human breast cancer samples and breast cancer cell lines. Using a loss-of-function approach, we showed that the downregulation of miR-196a inhibited the proliferation of breast cancer cells in vitro and in vivo. Ubiquitin-conjugating enzyme E2C (UBE2C) gene as a cellular proto-oncogene, which was overexpressed and positively correlated with miR-196a expression in breast cancer tissues, was identified as a direct target of miR-196a. Moreover, in order to investigate whether miR-196a regulated cell growth in breast cancer cells by targeting UBE2C, rescue studies were performed in breast cancer cells. The restoration of UBE2C by transfecting UBE2C cDNA in anti-miR-196a-transfected breast cancer cells rescued the suppression of cell proliferation. In conclusion, the present study showed that miR-196a promoted cell proliferation by targeting UBE2C in breast cancer. Thus, miR-196a may be a potential oncogene in breast cancer and a promising therapeutic target in breast cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinogenesis*
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • Mice
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Middle Aged
  • Protein Processing, Post-Translational / genetics
  • Proto-Oncogene Mas
  • Ubiquitin-Conjugating Enzymes / genetics*
  • Ubiquitin-Conjugating Enzymes / metabolism
  • Xenograft Model Antitumor Assays


  • MAS1 protein, human
  • MIRN196 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Mas
  • UBE2C protein, human
  • Ubiquitin-Conjugating Enzymes