MiR-34a inhibits proliferation and migration of breast cancer through down-regulation of Bcl-2 and SIRT1

Clin Exp Med. 2013 May;13(2):109-17. doi: 10.1007/s10238-012-0186-5. Epub 2012 May 24.


MicroRNA-34a(miR-34a), a pivotal member of the p53 network, was found to be down-regulated in multiple types of tumors and further reported as a tumor suppressor microRNA. However, the profile and biological effects of miR-34a in breast cancer are still unclear. In this study, we aimed to determine the effect of miR-34a on the growth of breast cancer and to investigate whether its effect is achieved by targeting Bcl-2 and SIRT1. We examined miR-34a levels in breast cancer cell lines and breast cancer specimens by qRT-PCR. Proliferation assay, apoptosis assay, and morphological monitoring were performed to assess the tumor suppression effect of miR-34a in breast cancer cell lines. Western blotting was used to identify the targets of miR-34a. We also investigated the anti-tumor effects of the treatment combining miR-34a with 5-FU in breast cancer cells. We found that miR-34a expression was down-regulated in 5 breast cancer cell lines compared with the immortalized normal mammary epithelial cell line 184A1, and was also down-regulated by almost 50 % in breast cancer samples compared with their corresponding adjacent non-malignant breast tissues. Ectopic restoration of miR-34a in breast cancer cells suppressed cells proliferation, invasion, and induced apoptosis. Bcl-2 and SIRT1 as the targets of miR-34a were found to be in reverse correlation with ectopic expression of miR-34a. Furthermore, the treatment combining miR-34a with 5-FU significantly showed more efficient anti-tumor effects than single treatment of miR-34a or 5-FU. Since miR-34a functions as tumor suppressor microRNA in breast cancer, modulating miR-34a level in breast cancer was suggested to be a new and useful approach of breast cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Down-Regulation
  • Drug Screening Assays, Antitumor
  • Female
  • Fluorouracil / pharmacology
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • MicroRNAs / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism*


  • Antineoplastic Agents
  • MIRN34 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • SIRT1 protein, human
  • Sirtuin 1
  • Fluorouracil