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Downregulation of eIF4G by microRNA-503 enhances drug sensitivity of MCF-7/ADR cells through suppressing the expression of ABC transport proteins

  • Authors:
    • Xia Pan
    • Xiaoyan Yang
    • Jinglei Zang
    • Si Zhang
    • Nan Huang
    • Xinxin Guan
    • Jianhua Zhang
    • Zhihui Wang
    • Xi Li
    • Xiaoyong Lei
  • View Affiliations / Copyright

    Affiliations: Institute of Pharmacy and Pharmacology, University of South China, Hengyang, Hunan 421001, P.R. China
    Copyright: © Pan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4785-4793
    |
    Published online on: April 19, 2017
       https://doi.org/10.3892/ol.2017.6049
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Abstract

Overexpression of adenosine triphosphate-binding cassette (ABC) transport protein is emerging as a critical contributor to anticancer drug resistance. The eukaryotic translation initiation factor (eIF) 4F complex, the key modulator of mRNA translation, is regulated by the phosphoinositide 3-kinase-AKT‑mammalian target of rapamycin pathway in anticancer drug‑resistant tumors. The present study demonstrated the roles of ABC translation protein alterations in the acquisition of the Adriamycin (ADM)‑resistant phenotype of MCF‑7 human breast cells. Quantitative polymerase chain reaction and western blot analysis were applied to examine the differences in mRNA and protein levels, respectively. It was found that the expression of the ABC sub‑family B member 1, ABC sub‑family C member 1 and ABC sub‑family G member 2 transport proteins were upregulated in MCF‑7/ADR cells. An MTT assay was used to detect the cell viability, from the results MCF‑7/ADR cells were less sensitive to ADM, tamoxifen (TAM) and taxol (TAX) treatment compared with MCF‑7 cells. We predicted that the 3'‑untranslated region of eukaryotic translation initiation factor 4‑γ 1 (eIF4G) contains a potential miRNA binding site for microRNA (miR)‑503 through using computational programs. These binding sites were confirmed by luciferase reporter assays. eIF4G mRNA degradation was accelerated in cells transfected with miR‑503 mimics. Furthermore, it was demonstrated that eIF4G and ABC translation proteins were significantly downregulated in MCF‑7/ADR cells after transfection with miR‑503. It was found that miR‑503 mimics could sensitize the cells to treatment with ADM, TAM and TAX. These findings demonstrated for the first time that eIF4G acted as a key factor in MCF‑7/ADR cells, and may be an efficient agent for preventing and reversing multi‑drug resistance in breast cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Pan X, Yang X, Zang J, Zhang S, Huang N, Guan X, Zhang J, Wang Z, Li X, Lei X, Lei X, et al: Downregulation of eIF4G by microRNA-503 enhances drug sensitivity of MCF-7/ADR cells through suppressing the expression of ABC transport proteins. Oncol Lett 13: 4785-4793, 2017.
APA
Pan, X., Yang, X., Zang, J., Zhang, S., Huang, N., Guan, X. ... Lei, X. (2017). Downregulation of eIF4G by microRNA-503 enhances drug sensitivity of MCF-7/ADR cells through suppressing the expression of ABC transport proteins. Oncology Letters, 13, 4785-4793. https://doi.org/10.3892/ol.2017.6049
MLA
Pan, X., Yang, X., Zang, J., Zhang, S., Huang, N., Guan, X., Zhang, J., Wang, Z., Li, X., Lei, X."Downregulation of eIF4G by microRNA-503 enhances drug sensitivity of MCF-7/ADR cells through suppressing the expression of ABC transport proteins". Oncology Letters 13.6 (2017): 4785-4793.
Chicago
Pan, X., Yang, X., Zang, J., Zhang, S., Huang, N., Guan, X., Zhang, J., Wang, Z., Li, X., Lei, X."Downregulation of eIF4G by microRNA-503 enhances drug sensitivity of MCF-7/ADR cells through suppressing the expression of ABC transport proteins". Oncology Letters 13, no. 6 (2017): 4785-4793. https://doi.org/10.3892/ol.2017.6049
Copy and paste a formatted citation
x
Spandidos Publications style
Pan X, Yang X, Zang J, Zhang S, Huang N, Guan X, Zhang J, Wang Z, Li X, Lei X, Lei X, et al: Downregulation of eIF4G by microRNA-503 enhances drug sensitivity of MCF-7/ADR cells through suppressing the expression of ABC transport proteins. Oncol Lett 13: 4785-4793, 2017.
APA
Pan, X., Yang, X., Zang, J., Zhang, S., Huang, N., Guan, X. ... Lei, X. (2017). Downregulation of eIF4G by microRNA-503 enhances drug sensitivity of MCF-7/ADR cells through suppressing the expression of ABC transport proteins. Oncology Letters, 13, 4785-4793. https://doi.org/10.3892/ol.2017.6049
MLA
Pan, X., Yang, X., Zang, J., Zhang, S., Huang, N., Guan, X., Zhang, J., Wang, Z., Li, X., Lei, X."Downregulation of eIF4G by microRNA-503 enhances drug sensitivity of MCF-7/ADR cells through suppressing the expression of ABC transport proteins". Oncology Letters 13.6 (2017): 4785-4793.
Chicago
Pan, X., Yang, X., Zang, J., Zhang, S., Huang, N., Guan, X., Zhang, J., Wang, Z., Li, X., Lei, X."Downregulation of eIF4G by microRNA-503 enhances drug sensitivity of MCF-7/ADR cells through suppressing the expression of ABC transport proteins". Oncology Letters 13, no. 6 (2017): 4785-4793. https://doi.org/10.3892/ol.2017.6049
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