MiR-15a is underexpressed and inhibits the cell cycle by targeting CCNE1 in breast cancer

Int J Oncol. 2013 Oct;43(4):1212-8. doi: 10.3892/ijo.2013.2034. Epub 2013 Jul 23.


MicroRNAs (miRNAs) are a small class of non-coding RNAs that are widely dysregulated in various cancers. They act as either oncogenes or tumor suppressor genes in human cancer. The purpose of this study was to examine the expression levels of miR-15a in human breast cancer and its potential role in disease pathogenesis. The expression levels of miR-15a were measured by quantitative polymerase chain reaction (qPCR) in 40 breast cancer specimens and adjacent normal breast tissues. MTT assays, colony formation assays, transwell chamber migration assays, cell cycle and apoptosis assays were used to explore the potential function of miR-15a in MDA-MB-231 human breast cancer cells. Luciferase reporter assays were performed to validate the regulation of a putative target of miR-15a, in corroboration with qPCR and western blot assays. We found that the expression of miR-15a was lower in breast cancer specimens compared with adjacent normal tissues (p<0.05). Overexpression of miR-15a inhibited cellular growth, suppressed migration and arrested cells at the G1 phase, but did not promote cellular apoptosis. Luciferase assays indicated that miR-15a can bind with its putative target site in the 3'-untranslated region (3'-UTR) of CCNE1, suggesting that CCNE1 is a direct target of miR-15a. qPCR and western blot analysis indicated that the overexpression of miR-15a results in the downregulation of CCNE1 at the mRNA and protein levels. Taken together, the upregulation of miR-15a expression causes cellular growth inhibition, suppression of migration and G1 phase arrest by targeting CCNE1. These findings suggest that miR-15a may act as a tumor suppressor gene in breast cancer and that, in the future, it could be used as a therapeutic target for the treatment of breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Cyclin E / antagonists & inhibitors
  • Cyclin E / genetics*
  • Cyclin E / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Oncogene Proteins / antagonists & inhibitors
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / metabolism
  • RNA, Messenger / genetics*


  • CCNE1 protein, human
  • Cyclin E
  • MIRN15 microRNA, human
  • MicroRNAs
  • Oncogene Proteins
  • RNA, Messenger