Downregulation of miR‑200c‑3p contributes to the resistance of breast cancer cells to paclitaxel by targeting SOX2

Oncol Rep. 2018 Dec;40(6):3821-3829. doi: 10.3892/or.2018.6735. Epub 2018 Sep 26.

Abstract

Acquisition of resistance to paclitaxel is a major obstacle to successful treatment of breast cancer patients, but the molecular mechanisms underlying the development of drug resistance remain largely unclear. The aim of the present study was to investigate the role and mechanism of action of miR‑200c‑3p in the resistance of breast cancer to paclitaxel. It was observed that miR‑200c‑3p expression, as determined by reverse transcription‑quantitative polymerase chain reaction analysis, was significantly downregulated in paclitaxel‑resistant MCF‑7/Tax cells compared with parental MCF‑7 cells. Overexpression of miR‑200c‑3p increased the chemosensitivity to paclitaxel and enhanced apoptosis in MCF‑7/Tax cells, whereas the downregulation of miR‑200c‑3p exerted the opposite effect. In addition, upregulation of miR‑200c‑3p in MCF‑7/Tax cells suppressed the expression of sex‑determining region Y‑box 2 (SOX2) at the mRNA and protein levels. Dual‑luciferase reporter assay demonstrated that SOX2 is a target of miR‑200c‑3p in MCF‑7/Tax cells. Moreover, knockdown of SOX2 expression increased chemosensitivity to paclitaxel and upregulated miR‑200c‑3p expression in MCF‑7/Tax cells. Taken together, the results of the present study indicated that miR‑200c‑3p plays a key role in the development of paclitaxel resistance in breast cancer, possibly partially through regulating SOX2 expression, suggesting that the miR‑200c‑3p‑SOX2 loop may serve as a potential target for the reversal of paclitaxel resistance in breast cancer.

MeSH terms

  • 3' Untranslated Regions
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Cell Proliferation
  • Cell Survival
  • Down-Regulation*
  • Drug Resistance, Neoplasm*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • Paclitaxel / pharmacology*
  • SOXB1 Transcription Factors / genetics*
  • SOXB1 Transcription Factors / metabolism

Substances

  • 3' Untranslated Regions
  • MIRN200 microRNA, human
  • MicroRNAs
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Paclitaxel