miR-34a sensitizes lung cancer cells to cisplatin via p53/miR-34a/MYCN axis

Biochem Biophys Res Commun. 2017 Jan 1;482(1):22-27. doi: 10.1016/j.bbrc.2016.11.037. Epub 2016 Nov 9.

Abstract

Cisplatin is the most potent and widespread used chemotherapy drug for lung cancer treatment. However, a large proportion of NSCLC patients were insensitive to chemotherapy. This study explored the role of miR-34a in regulating sensitivity of NSCLC cells to cisplatin and its downstream targets. The quantitative PCR result showed that miR-34a expression was upregulated in cisplatin sensitive NSCLC patients compared cisplatin insensitive NSCLC controls. By applying loss-and-gain function analysis, we demonstrated that miR-34a directly targeted to MYCN to sensitize NSCLC cells to cisplatin. In addition, p53 was found to monitor the expression of miR-34a in NSCLC cells after cisplatin treatment. Therefore, the sensitivity of cisplatin in NSCLC cells was modulated via p53/miR-34a/MYCN axis.

Keywords: Cisplatin; MYCN; NSCLC; miR-34a; p53.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cisplatin / pharmacology*
  • Drug Synergism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • MicroRNAs / metabolism*
  • N-Myc Proto-Oncogene Protein / metabolism*
  • Signal Transduction / drug effects
  • Treatment Outcome
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Antineoplastic Agents
  • MIRN34 microRNA, human
  • MYCN protein, human
  • MicroRNAs
  • N-Myc Proto-Oncogene Protein
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Cisplatin