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

Dong,Zuoliang; Ren,Li; Lin,Li; Li,Jiang; Huang,Yiwen; Li,Jinhong

doi:10.3892/mmr.2014.2662

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

Authors:
- Zuoliang Dong
- Li Ren
- Li Lin
- Jiang Li
- Yiwen Huang
- Jinhong Li
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Affiliations: Department of Clinical Laboratory, Tianjin Medical University General Hospital, Heping District, Tianjin 300052, P.R. China, 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, Department of Thoracic Oncology, Tianjin Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, Hexi 300060, P.R. China
Published online on: October 15, 2014 https://doi.org/10.3892/mmr.2014.2662
Pages: 682-690

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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.

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