Effect of miR-1244 on cisplatin-treated non-small cell lung cancer via MEF2D expression

Oncol Rep. 2017 Jun;37(6):3475-3483. doi: 10.3892/or.2017.5624. Epub 2017 May 4.

Abstract

The aim of this study was to investigate the function of miR-1244 in cisplatin-treated non-small cell lung cancer (NSCLC). The results of quantitative PCR analysis revealed that the expression levels of miR-1244 in cisplatin‑treated A549 and NCI-H522 human lung cancer cell lines were lower than those in untreated A549 and NCI-H522 cells. Similarly, the expression level of miR-1244 in NSCLC tissue samples from cisplatin-treated patients was also lower than that in non-cisplatin-treated NSCLC patients. Notably, the overall survival times of cisplatin-treated NSCLC patients with high miR-1244 expression were superior to those patients with low miR-1244 expression. We found that overexpression of miR-1244 suppressed cell viability and increased LDH toxicity in cisplatin-treated A549 and NCI-H522 cells. Additionally, overexpression of miR-1244 induced the apoptosis of cisplatin-treated A549 and NCI-H522 cells. Furthermore, overexpression of miR-1244 promoted caspase-3 activity and p53 and Bax protein expression, and suppressed myocyte enhancer factor 2D (MEF2D) and cyclin D1 protein expression in cisplatin‑treated A549 and NCI-H522 cells. Small interfering RNA (siRNA) targeting MEF2D suppressed the protein expression of MEF2D, and was able to decrease the proliferation, promote caspase-3 activity, p53 and Bax protein expression and inhibit cyclin D1 protein expression in cisplatin-treated A549 and NCI-H522 cells following the overexpression of miR-1244. In summary, we found that miR-1244 affected cisplatin-treated NSCLC via MEF2D expression.

MeSH terms

  • A549 Cells
  • Apoptosis / drug effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Caspase 3 / genetics
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cisplatin / administration & dosage*
  • Cisplatin / adverse effects
  • Cyclin D1 / genetics
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MEF2 Transcription Factors / genetics
  • MicroRNAs / genetics*
  • Tumor Suppressor Protein p53 / genetics
  • bcl-2-Associated X Protein / genetics

Substances

  • MEF2 Transcription Factors
  • MEF2D protein, human
  • MIRN1244 microRNA, human
  • MicroRNAs
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Cyclin D1
  • Caspase 3
  • Cisplatin