miR‑501‑3p sensitizes glioma cells to cisplatin by targeting MYCN

Mol Med Rep. 2018 Nov;18(5):4747-4752. doi: 10.3892/mmr.2018.9458. Epub 2018 Sep 5.

Abstract

Cisplatin, a commonly used chemotherapeutic agent for glioma patients, treatment often leads to chemoresistance. Accumulating evidence has demosntrated that microRNA (miRNA/miR) is involved in drug resistance of glioma cells. Nevertheless, the role of miR‑501‑3p in glioma cell resistance to cisplatin is unclear. In the present study, it was revealed that miR‑501‑3p expression was decreased in glioma tissues and further underexpressed in cisplatin‑resistant glioma cells compared with wild‑type (WT) glioma cells. Furthermore, cisplatin treatment inhibited the level of miR‑501‑3p in a time‑dependent way. Ectopic expression of miR‑501‑3p suppressed glioma cell growth and invasion, but increased cisplatin‑resistant glioma cell apoptosis. Furthermore, miR‑501‑3p sensitized glioma cells to cisplatin‑induced proliferation arrest and death. Mechanistically, it was demonstrated that miR‑501‑3p targeted MYCN in glioma cells. In addition, it was revealed that miR‑501‑3p inhibited MYCN expression by a luciferase reporter assay and reverse transcription‑quantitative polymerase chain reaction. Notably, restoration of MYCN reversed the effects of miR‑501‑3p in cisplatin‑resistant glioma cells. In conclusion, these results suggested that miR‑501‑3p may serve a promising marker for cisplatin resistance.

MeSH terms

  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / administration & dosage*
  • Cisplatin / adverse effects
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioma / drug therapy*
  • Glioma / genetics
  • Glioma / pathology
  • Humans
  • Male
  • MicroRNAs / genetics*
  • N-Myc Proto-Oncogene Protein / genetics*

Substances

  • MIRN501 microRNA, human
  • MYCN protein, human
  • MicroRNAs
  • N-Myc Proto-Oncogene Protein
  • Cisplatin