MiR-888 regulates side population properties and cancer metastasis in breast cancer cells

Biochem Biophys Res Commun. 2014 Aug 8;450(4):1234-40. doi: 10.1016/j.bbrc.2014.05.022. Epub 2014 May 15.

Abstract

Cancer stem cells (CSCs) have recently been reported to possess properties related to cancer metastasis. However, the mechanism by which microRNAs (miRNAs) regulate these properties remains unclear. This study aims to investigate a correlation between miRNAs and the side population (SP) of human breast cancer cell line MCF-7 with CSC properties. miR-888 was found in our previous study to be up-regulated in SP cells and predicted to target E-Cadherin directly, indicating a potential role in maintaining SP properties and regulating the epithelial-mesenchymal transition (EMT) and cancer metastasis. After the over-expression of miR-888 in MCF-7 cells and knock-down of its expression in SP cells, we found that miR-888 played a role in maintaining CSC-related properties. Next, miR-888 was found to regulate the EMT process by targeting related gene expression. Lastly, MCF-7 cells over-expressing miR-888 exhibited a significant reduction in their ability to adhere to the extracellular matrix and an increased potential for migration and invasion, whereas knock-down of miR-888 expression in SP cells reversed these trends. In conclusion, miR-888 maintains SP properties and regulates EMT and metastasis in MCF-7 cells, potentially by targeting E-Cadherin expression.

Keywords: Cancer metastasis; Cancer stem cells; Epithelial–mesenchymal transition; Side population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • DNA Primers
  • Epithelial-Mesenchymal Transition
  • Female
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Neoplasm Metastasis*
  • Real-Time Polymerase Chain Reaction

Substances

  • DNA Primers
  • MIRN888 microRNA, human
  • MicroRNAs