MicroRNA expression profiles of drug-resistance breast cancer cells and their exosomes

Oncotarget. 2016 Apr 12;7(15):19601-9. doi: 10.18632/oncotarget.7481.

Abstract

Exosomes have been shown to transmit drug resistance through delivering miRNAs. We aimed to explore their roles in breast cancer. Three resistant sublines were established by exposing parental MDA-MB-231 cell line to docetaxel, epirubicin and vinorelbine, respectively. Preneoadjuvant chemotherapy biopsies and paired surgically-resected specimens embedded in paraffin from 23 breast cancer patients were collected. MiRNA expression profiles of the cell lines and their exosomes were evaluated using microarray. The result showed that most miRNAs in exosomes had a lower expression level than that in cells, however, some miRNAs expressed higher in exosomes than in cells, suggesting a number of miRNAs is concentrated in exosomes. Among the dysregulated miRNAs, 22 miRNAs were consistently up-regulated in exosomes and their cells of origin. We further found that 12 of the 22 miRNAs were significantly up-regulated after preneoadjuvant chemotherapy. Further study of the role of these 12 miRNAs in acquisition of drug resistance is needed to clarify their contribution to chemoresistance.

Keywords: breast; cancer; chemoresistance; microRNA; microvesicles.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Docetaxel
  • Drug Resistance, Neoplasm / genetics*
  • Epirubicin / pharmacology
  • Exosomes / genetics*
  • Exosomes / ultrastructure
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Inhibitory Concentration 50
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • Microscopy, Electron
  • Taxoids / pharmacology
  • Vinblastine / analogs & derivatives
  • Vinblastine / pharmacology
  • Vinorelbine

Substances

  • Antineoplastic Agents
  • MicroRNAs
  • Taxoids
  • Docetaxel
  • Epirubicin
  • Vinblastine
  • Vinorelbine