MicroRNA-134 modulates resistance to doxorubicin in human breast cancer cells by downregulating ABCC1

Biotechnol Lett. 2015 Dec;37(12):2387-94. doi: 10.1007/s10529-015-1941-y. Epub 2015 Aug 29.

Abstract

Objectives: To investigate the role of microRNAs in doxorubicin resistance of breast cancer cells.

Results: MicroRNA-134 was down-regulated in doxorubicin-resistant and doxorubicin-sensitive breast cancer samples and MCF-7/ADR cell lines. After transfection of miR-134 mimics, an MTT assay confirmed that the MCF-7/ADR cell proliferation was inhibited. In the presence of doxorubicin, there was inhibition of cell proliferation. Transfection of miR-134 mimics induced MCF-7/ADR cell apoptosis. The expression of ABCC1 was significantly upregulated in doxorubicin-resistant or -sensitive breast cancer tissues and MCF-7/ADR cell lines. Over-expression of miR-134 decreased the expression of ABCC1 at the protein level.

Conclusion: MicroRNA-134 modulates resistance to doxorubicin in breast cancer cells by downregulating the expression of ABCC1 which is known to encode the multidrug resistance-associated protein 1.

Keywords: ABCC1; Breast cancer; Doxorubicin; Doxorubicin resistance; Drug resistance; MRP1; MicroRNA-134.

MeSH terms

  • Antibiotics, Antineoplastic / metabolism*
  • Breast Neoplasms / physiopathology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Down-Regulation*
  • Doxorubicin / metabolism*
  • Drug Resistance, Neoplasm*
  • Formazans / analysis
  • Humans
  • MicroRNAs / metabolism*
  • Models, Biological
  • Multidrug Resistance-Associated Proteins / biosynthesis*
  • Tetrazolium Salts / analysis

Substances

  • Antibiotics, Antineoplastic
  • Formazans
  • MIRN134 microRNA, human
  • MicroRNAs
  • Multidrug Resistance-Associated Proteins
  • Tetrazolium Salts
  • MTT formazan
  • Doxorubicin
  • multidrug resistance-associated protein 1