Effect of microRNA-21 on multidrug resistance reversal in A549/DDP human lung cancer cells

Mol Med Rep. 2015 Jan;11(1):682-90. doi: 10.3892/mmr.2014.2662. Epub 2014 Oct 15.


Lung cancer is a predominant cause of cancer-related mortality and numerous lung cancer patients succumb to the disease due to drug resistance. A number of microRNAs (miRNAs) are upregulated in cancer and are involved in tumorigenesis, functioning as oncogenes. Several functional studies have shown that miR-21 is important in carcinogenesis; however, none of these studies has investigated multidrug resistance (MDR) reversal in human lung cancer cells. In the present study, the effect of miR-21 on MDR reversal was analyzed in A549/DDP lung cancer cells. The data demonstrated the following after miR-21 silencing: Proliferation of the tumor cells was inhibited, cell apoptosis and oxidative damage were increased, the cell cycle was blocked at the G0/G1 phase, expression levels of P-glycoprotein were reduced, accumulation of Rhodamine 123 was increased, and the MDR-related genes encoding MDR1, MPR, glutathione S-transferase-π, B-cell lymphoma 2, cyclin-dependent kinase 1, cystathione and glutathione were downregulated. Further mechanistic analysis revealed that miR-21 silencing reduced AKT phosphorylation and transcriptional activation of E2F-1 and Twist. In conclusion, this study demonstrated that miR-21 silencing reversed lung cancer cell MDR by modulation of MDR-related gene expression and inhibition of the AKT signaling pathway, suggesting that miR-21 may be a potential therapeutic candidate in patients with MDR lung cancer.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Apoptosis / genetics
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Survival / genetics
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Silencing
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • MicroRNAs / genetics*
  • Neoplasm Metastasis
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics
  • Signal Transduction


  • ATP Binding Cassette Transporter, Subfamily B
  • MIRN21 microRNA, human
  • MicroRNAs
  • Cisplatin