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Low expression of PRKCDBP promoted cisplatin resistance in lung adenocarcinoma by DNMT1 and TNF‑α

  • Authors:
    • Jiali Fu
    • Huixin Zhou
    • Jie Chen
    • Yumin Wang
  • View Affiliations / Copyright

    Affiliations: Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China, Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China
    Copyright: © Fu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1616-1626
    |
    Published online on: August 7, 2020
       https://doi.org/10.3892/or.2020.7721
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Abstract

The aim of the present study was to explore the mechanism of protein kinase C delta binding protein (PRKCDBP) promoting cisplatin resistance in lung adenocarcinoma (LAD). The PRKCDBP expression level was herein detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). We overexpressed PRKCDBP and tumor necrosis factor‑α (TNF‑α) in A549/DDP cell line, DNMT1 in A549 cells and siRNA TNF‑α in A549 cells with lentivirus‑mediated technique, and then, analyzed their biological diversification. The results showed a significantly lower expression level of PRKCDBP was lowly expressed in the A549/DDP cell line and LAD tissues than that in A549 cells and adjacent cancer tissues (P<0.05 and P<0.01), while the DNMT1 mRNA level was remarkably increased (P=0.000) and the promoter of PRKCDBP was hypermethylated in the A549/DDP cell line. Additionally, DNMT1 mRNA level in cisplatin‑insensitive group was markedly higher than that in cisplatin‑sensitive group (t=7.233, P<0.0001), while PRKCDBP mRNA level in cisplatin insensitive group was notably lower than that in cisplatin‑sensitive group (t=8.784, P<0.0001). The results showed that PRKCDBP mRNA level was significantly elevated following treatment with 5 µM decitabine for 24 h (P<0.0001), while the DNMT1 mRNA level was notably reduced (P=0.000). When PRKCDBP was overexpressed, the DNMT1 mRNA level was markedly decreased (P=0.007), the rate of proliferation (P<0.05 or P<0.01), IC50 of cisplatin (P<0.001), G2/M phase and S phase cells were obviously reduced (P<0.001), while G0/G1 phase cells, apoptosis (P<0.001) distinctly increased, but migration ability did not significantly change. TNF‑α overexpression resulted in an increase of PRKCDBP mRNA level (P<0.001), while TNF‑α siRNA led to PRKCDBP mRNA level distinctly reduced (P<0.001). Overexpression of DNMT1 improved IC50 in A549 cells. Thus, findings of the present study ascertained the promoter of PRKCDBP was hypermethylated in A549/DDP cells. In conclusion, low expression of PRKCDBP promoted cisplatin resistance in LAD by DNMT1 and TNF‑α.
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Copy and paste a formatted citation
Spandidos Publications style
Fu J, Zhou H, Chen J and Wang Y: Low expression of PRKCDBP promoted cisplatin resistance in lung adenocarcinoma by DNMT1 and TNF‑α. Oncol Rep 44: 1616-1626, 2020.
APA
Fu, J., Zhou, H., Chen, J., & Wang, Y. (2020). Low expression of PRKCDBP promoted cisplatin resistance in lung adenocarcinoma by DNMT1 and TNF‑α. Oncology Reports, 44, 1616-1626. https://doi.org/10.3892/or.2020.7721
MLA
Fu, J., Zhou, H., Chen, J., Wang, Y."Low expression of PRKCDBP promoted cisplatin resistance in lung adenocarcinoma by DNMT1 and TNF‑α". Oncology Reports 44.4 (2020): 1616-1626.
Chicago
Fu, J., Zhou, H., Chen, J., Wang, Y."Low expression of PRKCDBP promoted cisplatin resistance in lung adenocarcinoma by DNMT1 and TNF‑α". Oncology Reports 44, no. 4 (2020): 1616-1626. https://doi.org/10.3892/or.2020.7721
Copy and paste a formatted citation
x
Spandidos Publications style
Fu J, Zhou H, Chen J and Wang Y: Low expression of PRKCDBP promoted cisplatin resistance in lung adenocarcinoma by DNMT1 and TNF‑α. Oncol Rep 44: 1616-1626, 2020.
APA
Fu, J., Zhou, H., Chen, J., & Wang, Y. (2020). Low expression of PRKCDBP promoted cisplatin resistance in lung adenocarcinoma by DNMT1 and TNF‑α. Oncology Reports, 44, 1616-1626. https://doi.org/10.3892/or.2020.7721
MLA
Fu, J., Zhou, H., Chen, J., Wang, Y."Low expression of PRKCDBP promoted cisplatin resistance in lung adenocarcinoma by DNMT1 and TNF‑α". Oncology Reports 44.4 (2020): 1616-1626.
Chicago
Fu, J., Zhou, H., Chen, J., Wang, Y."Low expression of PRKCDBP promoted cisplatin resistance in lung adenocarcinoma by DNMT1 and TNF‑α". Oncology Reports 44, no. 4 (2020): 1616-1626. https://doi.org/10.3892/or.2020.7721
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