title: Effect of microRNA-21 on multidrug resistance reversal in A549/DDP human lung cancer cells.
abstract: 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.
authors.affiliation: Department of Clinical Laboratory, Tianjin Medical University General Hospital, Heping District, Tianjin 300052, P.R. China.
authors.forename: Zuoliang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Clinical Laboratory, Key Laboratory of Cancer Prevention and Therapy, Tianjin Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, Hexi 300060, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Ren
authors.affiliation: Department of Thoracic Oncology, Tianjin Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, Hexi 300060, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Clinical Laboratory, Tianjin Medical University General Hospital, Heping District, Tianjin 300052, P.R. China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, Tianjin Medical University General Hospital, Heping District, Tianjin 300052, P.R. China.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Clinical Laboratory, Tianjin Medical University General Hospital, Heping District, Tianjin 300052, P.R. China.
authors.forename: Jinhong
authors.initials: J
authors.lastname: Li
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D002945:Cisplatin