Effect of microRNA-21 on multidrug resistance reversal in A549/DDP human lung cancer cells
| Autor: | Jiang Li, Li Ren, Zuoliang Dong, Li Lin, Yiwen Huang, Jinhong Li |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
ATP Binding Cassette Transporter Subfamily B Lung Neoplasms Cell Survival Apoptosis Biology medicine.disease_cause Biochemistry Cell Line Tumor microRNA Genetics medicine Humans Gene silencing Gene Silencing Neoplasm Metastasis Lung cancer Molecular Biology Oncogene Akt/PKB signaling pathway Cell Cycle Cancer Cell cycle medicine.disease Molecular biology Gene Expression Regulation Neoplastic MicroRNAs Oxidative Stress Oncology Drug Resistance Neoplasm Molecular Medicine Cisplatin Carcinogenesis Oxidation-Reduction Signal Transduction |
| Zdroj: | Molecular Medicine Reports. 11:682-690 |
| ISSN: | 1791-3004 1791-2997 |
| DOI: | 10.3892/mmr.2014.2662 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|