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Article Open Access

Increased MIR31HG lncRNA expression increases gefitinib resistance in non-small cell lung cancer cell lines through the EGFR/PI3K/AKT signaling pathway

  • Authors:
    • Bing Wang
    • Hong Jiang
    • Limin Wang
    • Xueqin Chen
    • Kan Wu
    • Shirong Zhang
    • Shenglin Ma
    • Bing Xia
  • View Affiliations / Copyright

    Affiliations: Department of Radiation Oncology, Hangzhou First People's Hospital, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 310002, P.R. China, Department of Thoracic Surgery, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310002, P.R. China, Department of Respiration, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310002, P.R. China, Department of Medical Oncology, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310002, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3494-3500
    |
    Published online on: March 20, 2017
       https://doi.org/10.3892/ol.2017.5878
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Abstract

The aim of the present study was to gain insight into the molecular mechanism of gefitinib resistance in non-small cell lung cancer (NSCLC), and demonstrate whether long noncoding RNA (lncRNA) expression signatures differ between gefitinib‑sensitive PC9 and gefitinib-resistant PC9 (PC9‑R) cell lines. PC9 and PC9‑R cells were treated with gefitinib and, after 48 h, proliferation and apoptosis were analyzed using a Cell Counting Kit‑8 (CCK‑8) assay and flow cytometry. Microarray expression profiling of lncRNAs was undertaken in both PC9 and PC9‑R cells, and the expression profiles were verified by reverse transcription quantitative‑polymerase chain reaction. The EGFR/PI3K/AKT signaling pathway and mitochondrial apoptosis protein expression levels were assessed by western blot analysis. The PC9 cell line treated with gefitinib had a more significant effect on cell viability and apoptosis than the PC9‑R cell line (P<0.05). Expression of various lncRNAs differed significantly between the two cell lines, and MIR31HG expression in particular was significantly higher in PC9‑R cells. As expected, MIR31HG lncRNA knockdown sensitized PC9‑R cells to gefitinib, and further experiments revealed that turning off the EGFR/PI3K/AKT signaling pathway activated expression of p53 in PC9‑R cells transfected with si‑MIR31HG. Furthermore, PC9‑R cells transfected with si‑MIR31HG induced cell apoptosis through the mitochondrial apoptosis pathway, and arrested the cell cycle in the G0/G1 phase. The results of the current study suggest that MIR31HG lncRNA levels in PC9‑R cells are higher than in PC9 cells. Furthermore, overexpression of MIR31HG lncRNAs may contribute to gefitinib resistance in PC9‑R cells through the EGFR/PI3K/AKT pathway, which impacts on cell proliferation, apoptosis and the cell cycle. MIR31HG lncRNA may therefore be a novel candidate biomarker for future therapeutic strategies involving EGFR-TKIs.
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Copy and paste a formatted citation
Spandidos Publications style
Wang B, Jiang H, Wang L, Chen X, Wu K, Zhang S, Ma S and Xia B: Increased MIR31HG lncRNA expression increases gefitinib resistance in non-small cell lung cancer cell lines through the EGFR/PI3K/AKT signaling pathway. Oncol Lett 13: 3494-3500, 2017.
APA
Wang, B., Jiang, H., Wang, L., Chen, X., Wu, K., Zhang, S. ... Xia, B. (2017). Increased MIR31HG lncRNA expression increases gefitinib resistance in non-small cell lung cancer cell lines through the EGFR/PI3K/AKT signaling pathway. Oncology Letters, 13, 3494-3500. https://doi.org/10.3892/ol.2017.5878
MLA
Wang, B., Jiang, H., Wang, L., Chen, X., Wu, K., Zhang, S., Ma, S., Xia, B."Increased MIR31HG lncRNA expression increases gefitinib resistance in non-small cell lung cancer cell lines through the EGFR/PI3K/AKT signaling pathway". Oncology Letters 13.5 (2017): 3494-3500.
Chicago
Wang, B., Jiang, H., Wang, L., Chen, X., Wu, K., Zhang, S., Ma, S., Xia, B."Increased MIR31HG lncRNA expression increases gefitinib resistance in non-small cell lung cancer cell lines through the EGFR/PI3K/AKT signaling pathway". Oncology Letters 13, no. 5 (2017): 3494-3500. https://doi.org/10.3892/ol.2017.5878
Copy and paste a formatted citation
x
Spandidos Publications style
Wang B, Jiang H, Wang L, Chen X, Wu K, Zhang S, Ma S and Xia B: Increased MIR31HG lncRNA expression increases gefitinib resistance in non-small cell lung cancer cell lines through the EGFR/PI3K/AKT signaling pathway. Oncol Lett 13: 3494-3500, 2017.
APA
Wang, B., Jiang, H., Wang, L., Chen, X., Wu, K., Zhang, S. ... Xia, B. (2017). Increased MIR31HG lncRNA expression increases gefitinib resistance in non-small cell lung cancer cell lines through the EGFR/PI3K/AKT signaling pathway. Oncology Letters, 13, 3494-3500. https://doi.org/10.3892/ol.2017.5878
MLA
Wang, B., Jiang, H., Wang, L., Chen, X., Wu, K., Zhang, S., Ma, S., Xia, B."Increased MIR31HG lncRNA expression increases gefitinib resistance in non-small cell lung cancer cell lines through the EGFR/PI3K/AKT signaling pathway". Oncology Letters 13.5 (2017): 3494-3500.
Chicago
Wang, B., Jiang, H., Wang, L., Chen, X., Wu, K., Zhang, S., Ma, S., Xia, B."Increased MIR31HG lncRNA expression increases gefitinib resistance in non-small cell lung cancer cell lines through the EGFR/PI3K/AKT signaling pathway". Oncology Letters 13, no. 5 (2017): 3494-3500. https://doi.org/10.3892/ol.2017.5878
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