miR-93 and PTEN: Key regulators of doxorubicin-resistance and EMT in breast cancer

Oncol Rep. 2017 Oct;38(4):2401-2407. doi: 10.3892/or.2017.5859. Epub 2017 Jul 31.

Abstract

It is not well established whether miR-93 is involved in drug resistance and epithelial-mesenchymal transition (EMT) in breast cancer, and its underlying mechanism remains uncertain. In the present study, the expression differences of miR-93 between paired breast cancer tissues confirmed it is involved in the progression of breast cancer. Such a difference was also observed in doxorubicin-resistant and -sensitive cells. Overexpressed miR-93 in sensitive cells revealed increases in cellular proliferation and the expression levels of drug-resistant-related genes, and a decrease in sensitivity to doxorubicin. This demonstrated the relationship between miR-93 and breast cancer drug resistance. Simultaneously, EMT was confirmed in miR-93 overexpressing sensitive cells. This indicated the triadic relationship among miR-93, EMT and drug resistance in breast cancer. We applied the Dual-luciferase Reporter assay to expose the direct interaction between miR-93 and PTEN, which suggested that miR-93 contributes to inducing EMT and drug resistance of breast cancer cells by targeting PTEN.

MeSH terms

  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Proliferation / genetics
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Drug Resistance, Neoplasm / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • PTEN Phosphohydrolase / genetics*

Substances

  • MIRN93 microRNA, human
  • MicroRNAs
  • Doxorubicin
  • PTEN Phosphohydrolase
  • PTEN protein, human