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Knockdown of ETV4 promotes autophagy‑dependent apoptosis in GBM cells by reducing the transcriptional activation of EMP1

  • Authors:
    • Junxiang Wang
    • Chengfa Sun
    • Jian Li
    • Hua Jiang
    • Yun Qiu
    • Mingjie Gong
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, Changshu No. 2 People's Hospital, The Affiliated Changshu Hospital of Xuzhou Medical University, Changshu, Suzhou, Jiangsu 215500, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 41
    |
    Published online on: December 6, 2021
       https://doi.org/10.3892/ol.2021.13159
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Abstract

ETS variant transcription factor 4 (ETV4) is a common cancer‑promoting transcription factor and its expression has been found to be significantly upregulated in glioblastoma multiforme (GBM), as determined via analysis of the Gene Expression Profiling Interactive Analysis (GEPIA) database. In addition, our previous study demonstrated that ETV4 expression was highly positively correlated with epithelial membrane protein 1 (EMP1). The present study aimed to determine whether ETV4 could influence the activation of the PI3K/AKT/mTOR signaling pathway to affect the autophagy and apoptosis of GBM cells by regulating the transcriptional activity of EMP1. In addition to the analysis of the GEPIA database, the expression levels of ETV4 were also investigated in several different GBM cell lines. After interfering with the expression of ETV4, western blotting was used to detect the expression levels of autophagy‑ and apoptosis‑related proteins, and a TUNEL assay was used to detect the levels of cell apoptosis. Dual luciferase reporter and chromatin immunoprecipitation assays were used to verify the potential binding site of ETV4 on EMP1. Western blotting was also used to analyze the expression levels of PI3K/AKT/mTOR signaling pathway‑related proteins. The results of the current study revealed that the expression levels of ETV4 were significantly upregulated in GBM cell lines compared with those in normal glial cells. In the GBM cell line, LN‑229, ETV4 was discovered to bind to the EMP1 promoter and positively regulate the expression of EMP1. The knockdown of ETV4 expression inhibited the PI3K/AKT/mTOR signaling pathway activity to promote autophagy and apoptosis, and this effect could be partially reversed by overexpressing EMP1. In conclusion, these findings indicated that the knockdown of ETV4 in GBM cells may reduce the transcriptional activation of EMP1 and thereby inhibit PI3K/AKT/mTOR signaling pathway activity to promote autophagy and apoptosis. This provides a novel insight into potential strategies for the treatment of GBM via the induction of autophagy‑dependent apoptosis.
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Copy and paste a formatted citation
Spandidos Publications style
Wang J, Sun C, Li J, Jiang H, Qiu Y and Gong M: Knockdown of ETV4 promotes autophagy‑dependent apoptosis in GBM cells by reducing the transcriptional activation of EMP1. Oncol Lett 23: 41, 2022.
APA
Wang, J., Sun, C., Li, J., Jiang, H., Qiu, Y., & Gong, M. (2022). Knockdown of ETV4 promotes autophagy‑dependent apoptosis in GBM cells by reducing the transcriptional activation of EMP1. Oncology Letters, 23, 41. https://doi.org/10.3892/ol.2021.13159
MLA
Wang, J., Sun, C., Li, J., Jiang, H., Qiu, Y., Gong, M."Knockdown of ETV4 promotes autophagy‑dependent apoptosis in GBM cells by reducing the transcriptional activation of EMP1". Oncology Letters 23.2 (2022): 41.
Chicago
Wang, J., Sun, C., Li, J., Jiang, H., Qiu, Y., Gong, M."Knockdown of ETV4 promotes autophagy‑dependent apoptosis in GBM cells by reducing the transcriptional activation of EMP1". Oncology Letters 23, no. 2 (2022): 41. https://doi.org/10.3892/ol.2021.13159
Copy and paste a formatted citation
x
Spandidos Publications style
Wang J, Sun C, Li J, Jiang H, Qiu Y and Gong M: Knockdown of ETV4 promotes autophagy‑dependent apoptosis in GBM cells by reducing the transcriptional activation of EMP1. Oncol Lett 23: 41, 2022.
APA
Wang, J., Sun, C., Li, J., Jiang, H., Qiu, Y., & Gong, M. (2022). Knockdown of ETV4 promotes autophagy‑dependent apoptosis in GBM cells by reducing the transcriptional activation of EMP1. Oncology Letters, 23, 41. https://doi.org/10.3892/ol.2021.13159
MLA
Wang, J., Sun, C., Li, J., Jiang, H., Qiu, Y., Gong, M."Knockdown of ETV4 promotes autophagy‑dependent apoptosis in GBM cells by reducing the transcriptional activation of EMP1". Oncology Letters 23.2 (2022): 41.
Chicago
Wang, J., Sun, C., Li, J., Jiang, H., Qiu, Y., Gong, M."Knockdown of ETV4 promotes autophagy‑dependent apoptosis in GBM cells by reducing the transcriptional activation of EMP1". Oncology Letters 23, no. 2 (2022): 41. https://doi.org/10.3892/ol.2021.13159
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