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Deubiquitinating enzyme 4 facilitates chemoresistance in glioblastoma by inhibiting P53 activity

  • Authors:
    • Na Qin
    • Fengli Han
    • Li Li
    • Yingwei Ge
    • Wei Lin
    • Jiang Wang
    • Lin Wu
    • Gang Zhao
    • Yanchun Deng
    • Jian Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Neurology, The Fourth People's Hospital of Shaanxi, Xi'an, Shaanxi 710032, P.R. China, Department of Neurosurgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
    Copyright: © Qin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 958-964
    |
    Published online on: November 1, 2018
       https://doi.org/10.3892/ol.2018.9654
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Abstract

Glioblastoma is a malignant primary brain tumor with poor prognosis with a median survival of only 12‑15 months. The high mortality rate of this disease is mainly due to the chemoresistance resulting from various reasons. Ubiquitin‑specific protease 4 (USP4) has recently been found to be elevated in various types of cancer through regulating P53 activity. However, whether USP4 is responsible for chemoresistance in glioblastoma is not clear. In the present study, the expression of USP4 in glioblastoma tissues and cell lines, as well as its association with temozolomide (TMZ) chemoresistance was analyzed. The results demonstrated that USP4 was significantly upregulated in glioblastoma tissues and cell lines at the mRNA and protein levels. Notably, USP4 knockdown alone did not affect glioblastoma cell viability; however, when USP4 knockdown cells were treated with TMZ, the cell viability was decreased significantly. In addition, the results revealed that cleaved poly(ADP‑ribose) polymerase level increased when USP4 was knocked down in glioblastoma cells treated with TMZ. It was also observed that P53 was increased in U251 and U87 cells with USP4 knockdown. Following treatment with a P53 specific inhibitor, the results suggested that USP4 mediated chemoresistance through inhibiting apoptosis in a P53‑dependent manner. In conclusion, the data revealed the critical role of USP4 in TMZ resistance in glioblastoma and provided new insight for future drug development for the treatment of this disease.
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Copy and paste a formatted citation
Spandidos Publications style
Qin N, Han F, Li L, Ge Y, Lin W, Wang J, Wu L, Zhao G, Deng Y, Zhang J, Zhang J, et al: Deubiquitinating enzyme 4 facilitates chemoresistance in glioblastoma by inhibiting P53 activity. Oncol Lett 17: 958-964, 2019.
APA
Qin, N., Han, F., Li, L., Ge, Y., Lin, W., Wang, J. ... Zhang, J. (2019). Deubiquitinating enzyme 4 facilitates chemoresistance in glioblastoma by inhibiting P53 activity. Oncology Letters, 17, 958-964. https://doi.org/10.3892/ol.2018.9654
MLA
Qin, N., Han, F., Li, L., Ge, Y., Lin, W., Wang, J., Wu, L., Zhao, G., Deng, Y., Zhang, J."Deubiquitinating enzyme 4 facilitates chemoresistance in glioblastoma by inhibiting P53 activity". Oncology Letters 17.1 (2019): 958-964.
Chicago
Qin, N., Han, F., Li, L., Ge, Y., Lin, W., Wang, J., Wu, L., Zhao, G., Deng, Y., Zhang, J."Deubiquitinating enzyme 4 facilitates chemoresistance in glioblastoma by inhibiting P53 activity". Oncology Letters 17, no. 1 (2019): 958-964. https://doi.org/10.3892/ol.2018.9654
Copy and paste a formatted citation
x
Spandidos Publications style
Qin N, Han F, Li L, Ge Y, Lin W, Wang J, Wu L, Zhao G, Deng Y, Zhang J, Zhang J, et al: Deubiquitinating enzyme 4 facilitates chemoresistance in glioblastoma by inhibiting P53 activity. Oncol Lett 17: 958-964, 2019.
APA
Qin, N., Han, F., Li, L., Ge, Y., Lin, W., Wang, J. ... Zhang, J. (2019). Deubiquitinating enzyme 4 facilitates chemoresistance in glioblastoma by inhibiting P53 activity. Oncology Letters, 17, 958-964. https://doi.org/10.3892/ol.2018.9654
MLA
Qin, N., Han, F., Li, L., Ge, Y., Lin, W., Wang, J., Wu, L., Zhao, G., Deng, Y., Zhang, J."Deubiquitinating enzyme 4 facilitates chemoresistance in glioblastoma by inhibiting P53 activity". Oncology Letters 17.1 (2019): 958-964.
Chicago
Qin, N., Han, F., Li, L., Ge, Y., Lin, W., Wang, J., Wu, L., Zhao, G., Deng, Y., Zhang, J."Deubiquitinating enzyme 4 facilitates chemoresistance in glioblastoma by inhibiting P53 activity". Oncology Letters 17, no. 1 (2019): 958-964. https://doi.org/10.3892/ol.2018.9654
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