Upregulation of microRNA-34a enhances the DDP sensitivity of gastric cancer cells by modulating proliferation and apoptosis via targeting MET

Oncol Rep. 2016 Oct;36(4):2391-7. doi: 10.3892/or.2016.5016. Epub 2016 Aug 11.

Abstract

Cisplatin (DDP) based chemotherapy is still the main strategy of human gastric cancer (GC) treatment. However, drug resistance is a major obstacle for DDP chemotherapy. Recent studies indicated that the resistance could be modulated by the regulation of dysregulated microRNAs (miRs). Previous study also found miR-34a was associated with cell proliferation and apoptosis in human GC; however, the relationship between miR-34a and DDP resistance still remains unexplored. The purpose of this study was to investigate whether miR-34a is associated with DDP resistance in human GC cells. Our study found that the expression of miR-34a was significantly decreased in DDP resistance human GC tissues and DDP resistance human GC SGC7901/DDP cells compared with normal GC tissues and cells. Upregulation of miR-34a enhanced the DDP sensitivity of SGC7901/DDP cells to DDP through the inhibition of cell proliferation and induction of cell apoptosis; on the other hand downregulation of miR-34a could weaken the DDP sensitivity of SGC7901 cells to DDP. Further study found that MET was a direct target of miR-34a and the regulation of MET could affect the DDP sensitivity of SGC7901/DDP cells. Moreover, our study also indicated that up-regulation of miR-34a could decrease the expression of MET in SGC7901/DDP cells. Therefore, our findings suggested miR-34a could modulate human gastric cancer cell DDP sensitivity by regulation of cell proliferation and apoptosis via targeting MET, potentially benefiting human GC treatment in the future.

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / administration & dosage*
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Proto-Oncogene Proteins c-met / biosynthesis*
  • Proto-Oncogene Proteins c-met / genetics
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology

Substances

  • MIRN34 microRNA, human
  • MicroRNAs
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Cisplatin