Downregulated miR-495 [Corrected] Inhibits the G1-S Phase Transition by Targeting Bmi-1 in Breast Cancer

Medicine (Baltimore). 2015 May;94(21):e718. doi: 10.1097/MD.0000000000000718.


Bmi-1 (B cell-specific Moloney murine leukemia virus integration site 1) is upregulated in breast cancer and was involved in many malignant progressions of breast cells, including cell proliferation, stem cell pluripotency, and cancer initiation. However, the epigenetic regulatory mechanism of Bmi-1 in breast cancer remains unclear. After analysis of the ArrayExpress dataset GSE45666, we comparatively detected the expression levels of miR-495 in 9 examined breast cancer cell lines, normal breast epithelial cells and 8 pairs of fresh clinical tumor samples. Furthermore, to evaluate the effect of miR-495 on the progression of breast cancer, MCF-7 and MDA-MB-231 were transduced to stably overexpress miR-495. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, colony formation assays, 5-Bromo-2-deoxyUridine labeling and immunofluorescence, anchorage-independent growth ability assay, flow cytometry analysis, and luciferase assays were used to test the effect of miR-495 in MCF-7 and MDA-MB-231 cells in vitro. Xenografted tumor model was also used to evaluate the effect of miR-495 in breast cancer. Herein, we found that miR-495, a predicted regulator of Bmi-1, was frequently downregulated in malignant cells and tissues of breast. Upregulation of miR-495 significantly suppressed breast cancer cell proliferation and tumorigenicity via G1-S arrest. Further analysis revealed that miR-495 targeted Bmi-1 through its 3' untranslated region. Moreover, Bmi-1 could neutralize the suppressive effect of miR-495 on cell proliferation and tumorigenicity of breast cancer in vivo. These data suggested that miR-495 could inhibit the G1-S phase transition that leads to proliferation and tumorigenicity inhibition by targeting and suppressing Bmi-1 in breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / physiology
  • Animals
  • Blotting, Western
  • Breast Neoplasms / physiopathology*
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Disease Models, Animal
  • Down-Regulation
  • Female
  • Humans
  • MCF-7 Cells
  • Mice
  • MicroRNAs / metabolism*
  • Phase Transition
  • Polycomb Repressive Complex 1 / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Real-Time Polymerase Chain Reaction
  • Up-Regulation / physiology*


  • 3' Untranslated Regions
  • Bmi1 protein, mouse
  • MIRN495 microRNA, human
  • MIRN495 microRNA, mouse
  • MicroRNAs
  • Proto-Oncogene Proteins
  • Polycomb Repressive Complex 1