Pathologically decreased miR-26a antagonizes apoptosis and facilitates carcinogenesis by targeting MTDH and EZH2 in breast cancer

Carcinogenesis. 2011 Jan;32(1):2-9. doi: 10.1093/carcin/bgq209. Epub 2010 Oct 15.


The role of miR-26a in carcinogenesis appears to be a complicated one, in the sense that both oncogenic and tumor suppressive effects were reported in cancers such as glioblastoma and hepatocellular carcinoma, respectively. Here, we report for the first time that miR-26a is downregulated in breast cancer specimens and cell lines and its transient transfection initiates apoptosis of breast cancer cell line MCF7 cells. Furthermore, retrovirus-delivered miR-26a impairs the in vitro colony forming and in vivo tumor-loading ability of MCF7 cells. Subsequently, MTDH and EZH2 are identified as two direct targets of miR-26a and they are significantly upregulated in breast cancer. MCF7 xenografts with exogenous miR-26a show that a decrease in expression of both MTDH and EZH2 is accompanied by an increase in apoptosis. Moreover, knockdown of MTDH causes apoptosis while reexpression of MTDH partially reverses the proapoptotic effect of miR-26a in MCF7 cells. Our findings suggest that miR-26a functionally antagonizes human breast carcinogenesis by targeting MTDH and EZH2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Blotting, Western
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Adhesion Molecules / genetics*
  • Cell Adhesion Molecules / metabolism
  • Cell Transformation, Neoplastic / genetics
  • DNA Fragmentation
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Enhancer of Zeste Homolog 2 Protein
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Membrane Proteins
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Polycomb Repressive Complex 2
  • RNA-Binding Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Cell Adhesion Molecules
  • DNA-Binding Proteins
  • MIRN26A microRNA, human
  • MTDH protein, human
  • Membrane Proteins
  • MicroRNAs
  • RNA-Binding Proteins
  • Transcription Factors
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2