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Down-regulation of 14-3-3 zeta sensitizes human glioblastoma cells to apoptosis induction

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Abstract

Strong 14-3-3 zeta protein expression plays an important role in tumorigenesis, including in the maintenance of cell growth, resistance increase, and the prevention of apoptosis. In this study, we focus on two targets: (1) the expression of 14-3-3 zeta in the different grades of human astrocytoma (II–IV), (2) suppression of 14-3-3 zeta protein expression in glioblastoma derived astrocytes by 14-3-3 zeta shRNA lentiviral particles. The tissues of human astrocytoma were provided from 30 patients (ten of each grade of astrocytoma). Control tissues were obtained from the peritumoral brain zone of those patients with glioblastoma. The protein and mRNA expression levels of each astrocytoma grade were assessed via western blotting and RT-PCR, respectively. Results indicated that 14-3-3 zeta was significantly expressed in glioblastoma multiforme (grade IV) and 14-3-3 zeta expression levels enhanced according to the increase of astrocytoma malignancy. In the cellular study for knock down of the 14-3-3 zeta protein, surgical biopsy of glioblastoma was used to isolate primary astrocyte. Astrocytes were transduced with 14-3-3 zeta shRNA or non-targeted shRNA lentiviral particles. Furthermore, reduction of the 14-3-3 zeta protein expression in the astrocytes evaluated through qRT-PCR and western blot after transduction of 14-3-3 zeta shRNA lentiviral particles. Moreover, apoptosis properties, including DNA fragmentation and ratio increase of Bax/Bcl-2 were observed in astrocytes following reduction of 14-3-3 zeta protein expression. Further observation indicated that the mitochondrial pathway through release of cytochorome c and caspase-3 activity was involved in the apoptosis induction. Hence, this study demonstrates a key role of the 14-3-3 zeta protein in tumorigenesis but also indicates that 14-3-3 zeta can be considered as a target for the astrocytoma treatment specially glioblastoma.

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Funding

This study was funded by functional neurosurgery research center, Shahid Beheshti University of medical sciences (Grant Number: 11974).

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Authors and Affiliations

  1. Functional Neurosurgery Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mansoureh Hashemi, Alireza Zali, Saeed Oraee-Yazdani & Akhtar Akbari

  2. Department of Chemical Engineering, University of Louisville, Louisville, KY40292, USA

    Javad Hashemi

  3. Shohada Tajrish Hospital, Functional Neurosurgery Research Center, Shahrdari St, Tajrish Square, Tehran, 1989934148, Iran

    Mansoureh Hashemi

Authors
  1. Mansoureh Hashemi
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  2. Alireza Zali
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  3. Javad Hashemi
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  4. Saeed Oraee-Yazdani
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Correspondence to Mansoureh Hashemi.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in study according to the Ethical Commission of the Shahid Beheshti University of Medical Sciences. Ethical code of study is IR.SBMU.RETECH.REC.1396.744.

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Informed consent was obtained from all individual participants included in the study.

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Hashemi, M., Zali, A., Hashemi, J. et al. Down-regulation of 14-3-3 zeta sensitizes human glioblastoma cells to apoptosis induction. Apoptosis 23, 616–625 (2018). https://doi.org/10.1007/s10495-018-1476-5

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  • DOI: https://doi.org/10.1007/s10495-018-1476-5

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