Jagged2 promotes cancer stem cell properties of triple negative breast cancer cells and paclitaxel resistance via regulating microRNA-200

Eur Rev Med Pharmacol Sci. 2018 Sep;22(18):6008-6014. doi: 10.26355/eurrev_201809_15936.

Abstract

Objective: To investigate the role of Jagged2 in triple negative breast cancer (TNBC) and its underlying mechanism.

Patients and methods: Breast cancer tissues of patients diagnosed with TNBC in Fujian Medical University Affiliated MinDong Hospital from January 2015 to September 2017 were selected. TNBC patients were divided into the paclitaxel-resistant group (n=34) and non-resistance group (n=11). Jagged2 expression in paclitaxel-resistant group and non-resistance group before and after treatment was detected by quantitative Real-time-polymerase chain reaction (qRT-PCR), respectively. After Jagged2 knockdown in paclitaxel-resistant MDA-MB-231 cells (MDA-MB-231/TXR), expression of CD44+CD24-ESA+ subset was detected by flow cytometry. MicroRNA-200 expression was detected after Jagged2 knockdown in MDA-MB-231/TXR cells.

Results: Jagged2 was highly expressed in paclitaxel-resistant TNBC tissues and cells. Jagged2 expression was found to be associated with cancer stem cell (CSC) properties of TNBC cells. Knockdown of Jagged2 inhibited CSC properties and paclitaxel resistance, whereas upregulated microRNA-200 expression. The inhibited CSC properties and paclitaxel resistance induced by Jagged2 knockdown were reversed by microRNA-200 knockdown.

Conclusions: Jagged2 maintains CSC properties of TNBC cells and paclitaxel resistance via regulating microRNA-200.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Drug Resistance, Neoplasm*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Jagged-2 Protein / genetics*
  • MicroRNAs / genetics*
  • Neoplastic Stem Cells / metabolism*
  • Paclitaxel
  • Triple Negative Breast Neoplasms / genetics*
  • Up-Regulation

Substances

  • JAG2 protein, human
  • Jagged-2 Protein
  • MIRN200 microRNA, human
  • MicroRNAs
  • Paclitaxel