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Novel Concepts of Glioblastoma Therapy Concerning Its Heterogeneity
Article

GRPEL2 Knockdown Exerts Redox Regulation in Glioblastoma

1
Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
2
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, Taiwan
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Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
4
Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
5
Department of Biochemistry, National Defense Medical Center, Taipei 11490, Taiwan
*
Authors to whom correspondence should be addressed.
Academic Editor: Patrick Auberger
Int. J. Mol. Sci. 2021, 22(23), 12705; https://doi.org/10.3390/ijms222312705
Received: 14 October 2021 / Revised: 6 November 2021 / Accepted: 22 November 2021 / Published: 24 November 2021
Malignant brain tumors are responsible for catastrophic morbidity and mortality globally. Among them, glioblastoma multiforme (GBM) bears the worst prognosis. The GrpE-like 2 homolog (GRPEL2) plays a crucial role in regulating mitochondrial protein import and redox homeostasis. However, the role of GRPEL2 in human glioblastoma has yet to be clarified. In this study, we investigated the function of GRPEL2 in glioma. Based on bioinformatics analyses from the Cancer Gene Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we inferred that GRPEL2 expression positively correlates with WHO tumor grade (p < 0.001), IDH mutation status (p < 0.001), oligodendroglial differentiation (p < 0.001), and overall survival (p < 0.001) in glioma datasets. Functional validation in LN229 and GBM8401 GBM cells showed that GRPEL2 knockdown efficiently inhibited cellular proliferation. Moreover, GRPEL2 suppression induced cell cycle arrest at the sub-G1 phase. Furthermore, GRPEL2 silencing decreased intracellular reactive oxygen species (ROS) without impending mitochondria membrane potential. The cellular oxidative respiration measured with a Seahorse XFp analyzer exhibited a reduction of the oxygen consumption rate (OCR) in GBM cells by siGRPEL2, which subsequently enhanced autophagy and senescence in glioblastoma cells. Taken together, GRPEL2 is a novel redox regulator of mitochondria bioenergetics and a potential target for treating GBM in the future. View Full-Text
Keywords: GrpE-like 2 homolog (GRPEL2); glioblastoma; oxygen consumption rate (OCR); autophagy; senescence GrpE-like 2 homolog (GRPEL2); glioblastoma; oxygen consumption rate (OCR); autophagy; senescence
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MDPI and ACS Style

Tang, C.-T.; Li, Y.-F.; Chou, C.-H.; Huang, L.-C.; Huang, S.-M.; Hueng, D.-Y.; Tsai, C.-K.; Chen, Y.-H. GRPEL2 Knockdown Exerts Redox Regulation in Glioblastoma. Int. J. Mol. Sci. 2021, 22, 12705. https://doi.org/10.3390/ijms222312705

AMA Style

Tang C-T, Li Y-F, Chou C-H, Huang L-C, Huang S-M, Hueng D-Y, Tsai C-K, Chen Y-H. GRPEL2 Knockdown Exerts Redox Regulation in Glioblastoma. International Journal of Molecular Sciences. 2021; 22(23):12705. https://doi.org/10.3390/ijms222312705

Chicago/Turabian Style

Tang, Chi-Tun, Yao-Feng Li, Chung-Hsing Chou, Li-Chun Huang, Shih-Ming Huang, Dueng-Yuan Hueng, Chia-Kuang Tsai, and Yuan-Hao Chen. 2021. "GRPEL2 Knockdown Exerts Redox Regulation in Glioblastoma" International Journal of Molecular Sciences 22, no. 23: 12705. https://doi.org/10.3390/ijms222312705

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