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Role of the SPI1/CDKN2A/p53 signaling pathway in cuproptosis of lung adenocarcinoma cells

  • Authors:
    • Jiayue An
    • Wei Song
    • Qin Wang
    • Boyu Tan
    • Xuan Fei
    • Ruoxi Wang
    • Siyan Li
    • Xiyu Lu
    • Youjie Li
    • Ning Xie
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Laboratory, The Second Medical College of Binzhou Medical University, Yantai, Shandong 264100, P.R. China, Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China, Department of Thoracic Surgery, Yantaishan Hospital Affiliated to Binzhou Medical University, Yantai, Shandong 264003, P.R. China
    Copyright: © An et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 353
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    Published online on: May 19, 2025
       https://doi.org/10.3892/ol.2025.15099
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Abstract

Lung adenocarcinoma (LUAD) is among the most prevalent malignancies worldwide. Cuproptosis, a copper‑induced form of cell death, has been identified as a key process in LUAD progression; however, the molecular mechanisms underlying cuproptosis in LUAD and potential therapeutic targets remain unclear. The present study utilized The Cancer Genome Atlas database to retrieve mRNA expression profiles and clinical information of LUAD, identifying 10 candidate genes from differentially expressed genes associated with cuproptosis. Protein‑protein interaction analysis indicated that CDK inhibitor 2A (CDKN2A), an upregulated gene in LUAD, may function as a hub gene. Furthermore, multiple online databases were used to analyze Spi‑1 proto‑oncogene (SPI1), a transcription factor upstream of CDKN2A, which was downregulated in LUAD cuproptosis. The LinkedOmics database identified the p53‑mediated cuproptosis‑related pathway regulated by CDKN2A. Gene expression patterns were examined through Gene Expression Profiling Interactive Analysis, the Human Protein Atlas and reverse transcription‑quantitative polymerase chain reaction. Prognostic significance was assessed using the UALCAN and Kaplan‑Meier plotter databases. In vitro experiments demonstrated that CDKN2A knockdown and SPI1 overexpression inhibited the proliferation and migration of the H1975 cell line. After copper‑induced cuproptosis in H1975 cells, SPI1 expression was upregulated, whereas CDKN2A expression was downregulated. When H1975 cells were pretreated with tetrathiomolybdate, the upregulation of SPI1 was inhibited and the downregulation of CDKN2A was also suppressed. Cell Counting Kit‑8 assays indicated that SPI1 overexpression and CDKN2A knockdown facilitated elesclomol‑CuCl2‑induced cuproptosis. Western blot analysis revealed an inverse association between SPI1 overexpression and CDKN2A/p53 levels. In conclusion, the present study demonstrated the role of the SPI1/CDKN2A/p53 axis in LUAD cuproptosis, providing insights into potential therapeutic targets and contributing to clinical research on treatment strategies.
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Copy and paste a formatted citation
Spandidos Publications style
An J, Song W, Wang Q, Tan B, Fei X, Wang R, Li S, Lu X, Li Y, Xie N, Xie N, et al: Role of the SPI1/CDKN2A/p53 signaling pathway in cuproptosis of lung adenocarcinoma cells. Oncol Lett 30: 353, 2025.
APA
An, J., Song, W., Wang, Q., Tan, B., Fei, X., Wang, R. ... Xie, N. (2025). Role of the SPI1/CDKN2A/p53 signaling pathway in cuproptosis of lung adenocarcinoma cells. Oncology Letters, 30, 353. https://doi.org/10.3892/ol.2025.15099
MLA
An, J., Song, W., Wang, Q., Tan, B., Fei, X., Wang, R., Li, S., Lu, X., Li, Y., Xie, N."Role of the SPI1/CDKN2A/p53 signaling pathway in cuproptosis of lung adenocarcinoma cells". Oncology Letters 30.1 (2025): 353.
Chicago
An, J., Song, W., Wang, Q., Tan, B., Fei, X., Wang, R., Li, S., Lu, X., Li, Y., Xie, N."Role of the SPI1/CDKN2A/p53 signaling pathway in cuproptosis of lung adenocarcinoma cells". Oncology Letters 30, no. 1 (2025): 353. https://doi.org/10.3892/ol.2025.15099
Copy and paste a formatted citation
x
Spandidos Publications style
An J, Song W, Wang Q, Tan B, Fei X, Wang R, Li S, Lu X, Li Y, Xie N, Xie N, et al: Role of the SPI1/CDKN2A/p53 signaling pathway in cuproptosis of lung adenocarcinoma cells. Oncol Lett 30: 353, 2025.
APA
An, J., Song, W., Wang, Q., Tan, B., Fei, X., Wang, R. ... Xie, N. (2025). Role of the SPI1/CDKN2A/p53 signaling pathway in cuproptosis of lung adenocarcinoma cells. Oncology Letters, 30, 353. https://doi.org/10.3892/ol.2025.15099
MLA
An, J., Song, W., Wang, Q., Tan, B., Fei, X., Wang, R., Li, S., Lu, X., Li, Y., Xie, N."Role of the SPI1/CDKN2A/p53 signaling pathway in cuproptosis of lung adenocarcinoma cells". Oncology Letters 30.1 (2025): 353.
Chicago
An, J., Song, W., Wang, Q., Tan, B., Fei, X., Wang, R., Li, S., Lu, X., Li, Y., Xie, N."Role of the SPI1/CDKN2A/p53 signaling pathway in cuproptosis of lung adenocarcinoma cells". Oncology Letters 30, no. 1 (2025): 353. https://doi.org/10.3892/ol.2025.15099
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