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Article

Inhibition of miR-23a increases the sensitivity of lung cancer stem cells to erlotinib through PTEN/PI3K/Akt pathway

  • Authors:
    • Zhijun Han
    • Xiaoyun Zhou
    • Shanqing Li
    • Yingzhi Qin
    • Yeye Chen
    • Hongsheng Liu
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic Surgery, Peking Union Medical College Hospital (PUMCH), Beijing 100730, P.R. China
  • Pages: 3064-3070
    |
    Published online on: September 4, 2017
       https://doi.org/10.3892/or.2017.5938
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Abstract

Epidermal growth factor receptor-targeted tyrosine kinase inhibitors (EGFR-TKIs) have become first-line drugs used for non-small cell lung cancer (NSCLC) treatment. However, drug resistance to EGFR-TKIs will be developed inevitably due to the repeated use of these drugs. In the present study, we isolated cancer stem cells (CSCs) from the PC9 NSCLC cell line. We then observed that the PC9 CSCs showed significant resistance to erlotinib compared with the PC9 non-CSCs. Erlotinib failed to suppress the phosphorylation of PI3K and AKT in PC9 CSCs, although the EGFR was inhibited sufficiently. Mechanically, we observed aberrant upregulation of microRNA-23a (miR-23a) and downregulation of PTEN in PC9 CSCs compared to PC9 non-CSCs. Luciferase reporter assays proved that PTEN was the target of miR-23a in PC9 CSCs. Furthermore, knockdown of miR-23a enhanced the antitumor effect of erlotinib by increasing the expression of PTEN. In addition, transfection with miR-23a inhibitors promoted the erlotinib-dependent inhibition of PI3K/AKT pathway, thus, suppressing the proliferation and inducing apoptosis in PC9 CSCs. These results propose that upregulation of miR-23a is a potential mechanism associated with resistance to EGFR-TKIs in lung cancer stem cells. Inhibition of miR-23a serves as a novel therapeutic strategy to eliminate the EGFR-TKIs resistance of lung cancer stem cells.
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Copy and paste a formatted citation
Spandidos Publications style
Han Z, Zhou X, Li S, Qin Y, Chen Y and Liu H: Inhibition of miR-23a increases the sensitivity of lung cancer stem cells to erlotinib through PTEN/PI3K/Akt pathway. Oncol Rep 38: 3064-3070, 2017.
APA
Han, Z., Zhou, X., Li, S., Qin, Y., Chen, Y., & Liu, H. (2017). Inhibition of miR-23a increases the sensitivity of lung cancer stem cells to erlotinib through PTEN/PI3K/Akt pathway. Oncology Reports, 38, 3064-3070. https://doi.org/10.3892/or.2017.5938
MLA
Han, Z., Zhou, X., Li, S., Qin, Y., Chen, Y., Liu, H."Inhibition of miR-23a increases the sensitivity of lung cancer stem cells to erlotinib through PTEN/PI3K/Akt pathway". Oncology Reports 38.5 (2017): 3064-3070.
Chicago
Han, Z., Zhou, X., Li, S., Qin, Y., Chen, Y., Liu, H."Inhibition of miR-23a increases the sensitivity of lung cancer stem cells to erlotinib through PTEN/PI3K/Akt pathway". Oncology Reports 38, no. 5 (2017): 3064-3070. https://doi.org/10.3892/or.2017.5938
Copy and paste a formatted citation
x
Spandidos Publications style
Han Z, Zhou X, Li S, Qin Y, Chen Y and Liu H: Inhibition of miR-23a increases the sensitivity of lung cancer stem cells to erlotinib through PTEN/PI3K/Akt pathway. Oncol Rep 38: 3064-3070, 2017.
APA
Han, Z., Zhou, X., Li, S., Qin, Y., Chen, Y., & Liu, H. (2017). Inhibition of miR-23a increases the sensitivity of lung cancer stem cells to erlotinib through PTEN/PI3K/Akt pathway. Oncology Reports, 38, 3064-3070. https://doi.org/10.3892/or.2017.5938
MLA
Han, Z., Zhou, X., Li, S., Qin, Y., Chen, Y., Liu, H."Inhibition of miR-23a increases the sensitivity of lung cancer stem cells to erlotinib through PTEN/PI3K/Akt pathway". Oncology Reports 38.5 (2017): 3064-3070.
Chicago
Han, Z., Zhou, X., Li, S., Qin, Y., Chen, Y., Liu, H."Inhibition of miR-23a increases the sensitivity of lung cancer stem cells to erlotinib through PTEN/PI3K/Akt pathway". Oncology Reports 38, no. 5 (2017): 3064-3070. https://doi.org/10.3892/or.2017.5938
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