Open Access

NQO1 drives glioblastoma cell aggressiveness through EMT induction via the PI3K/Akt/mTOR/Snail pathway

  • Authors:
    • Lan Zheng
    • Shipeng Yang
    • Ran Xu
    • Yang Yang
    • Jishu Quan
    • Zhenhua Lin
    • Chunhua Quan
  • View Affiliations

  • Published online on: August 8, 2023     https://doi.org/10.3892/ijo.2023.5558
  • Article Number: 110
  • Copyright: © Zheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Glioblastoma multiforme (GBM) is the most frequent and lethal cancer derived from the central nervous system, of which the mesenchymal (MES) subtype seriously influences the survival and prognosis of patients. NAD(P)H: quinone acceptor oxidoreductase 1 (NQO1) serves an important role in the carcinogenesis and progression of various types of cancer; however, the specific mechanism underlying the regulatory effects of NQO1 on GBM is unclear. Thus, the present study aimed to explore the role and mechanism of NQO1 in GBM progression. The results of bioinformatics analysis and immunohistochemistry showed that high expression of NQO1 was significantly related to the MES phenotype of GBM and shorter survival. In addition, MTT, colony formation, immunofluorescence and western blot analyses, and lung metastasis model experiments suggested that silencing NQO1 inhibited the proliferation and metastasis of GBM cells in vitro and in vivo. Furthermore, western blotting showed that the activity of the PI3K/Akt/mTOR signaling pathway was revealed to be inhibited by downregulation of NQO1 expression, whereas it was enhanced by overexpression of NQO1. Notably, co‑immunoprecipitation and ubiquitination experiments suggested that Snail was considered an important downstream target of NQO1 in GBM cells. Snail knockdown could eliminate the promoting effect of ectopic NQO1 on the proliferation and invasion of GBM cells, and reduce its effects on the activity of PI3K/Akt/mTOR signaling pathway. These results indicated that NQO1 could promote GBM aggressiveness by activating the PI3K/Akt/mTOR signaling pathway in a Snail‑dependent manner, and NQO1 and its relevant pathways may be considered novel targets for GBM therapy.
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October-2023
Volume 63 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Copy and paste a formatted citation
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Spandidos Publications style
Zheng L, Yang S, Xu R, Yang Y, Quan J, Lin Z and Quan C: NQO1 drives glioblastoma cell aggressiveness through EMT induction via the PI3K/Akt/mTOR/Snail pathway. Int J Oncol 63: 110, 2023.
APA
Zheng, L., Yang, S., Xu, R., Yang, Y., Quan, J., Lin, Z., & Quan, C. (2023). NQO1 drives glioblastoma cell aggressiveness through EMT induction via the PI3K/Akt/mTOR/Snail pathway. International Journal of Oncology, 63, 110. https://doi.org/10.3892/ijo.2023.5558
MLA
Zheng, L., Yang, S., Xu, R., Yang, Y., Quan, J., Lin, Z., Quan, C."NQO1 drives glioblastoma cell aggressiveness through EMT induction via the PI3K/Akt/mTOR/Snail pathway". International Journal of Oncology 63.4 (2023): 110.
Chicago
Zheng, L., Yang, S., Xu, R., Yang, Y., Quan, J., Lin, Z., Quan, C."NQO1 drives glioblastoma cell aggressiveness through EMT induction via the PI3K/Akt/mTOR/Snail pathway". International Journal of Oncology 63, no. 4 (2023): 110. https://doi.org/10.3892/ijo.2023.5558