CREBRF is a potent tumor suppressor of glioblastoma by blocking hypoxia-induced autophagy via the CREB3/ATG5 pathway

Xue,Hao; Zhang,Jinsen; Guo,Xing; Wang,Jian; Li,Jiangbing; Gao,Xiao; Guo,Xiaofan; Li,Tong; Xu,Shugang; Zhang,Ping; Liu,Qinglin; Li,Gang

doi:10.3892/ijo.2016.3576

CREBRF is a potent tumor suppressor of glioblastoma by blocking hypoxia-induced autophagy via the CREB3/ATG5 pathway

Authors:
- Hao Xue
- Jinsen Zhang
- Xing Guo
- Jian Wang
- Jiangbing Li
- Xiao Gao
- Xiaofan Guo
- Tong Li
- Shugang Xu
- Ping Zhang
- Qinglin Liu
- Gang Li
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Affiliations: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Biomedicine, University of Bergen, 5009 Bergen, Norway, Department of Cardiology, Shandong Provincial Hospital of Shandong University, Jinan, Shandong 250021, P.R. China, Brain Science Research Institute, Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: June 9, 2016 https://doi.org/10.3892/ijo.2016.3576
Pages: 519-528

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Abstract

Hypoxia induces protective autophagy in advanced glioblastoma cells, and targeting this process may improve the outcome for glioblastoma patients. Recent studies have suggested that the autophagic process is upregulated in glioblastoma cells in response to extensive hypoxia. Here, we describe a novel tumor suppressor in glioblastoma cells, whereby hypoxia downregulated CREBRF expression and acts as a potent inhibitor of autophagy in glioblastoma cells via the CREB3/ATG5 pathway. Our results demonstrate that CREBRF expression negatively correlates with autophagic and HIF-1α levels in different grade gliomas. Given that CREBRF is a negative regulator of CREB3, CREB3 knockdown also repressed hypoxia-induced autophagy in glioblastoma cells in vitro. Collectively, our findings provide new insight into the molecular mechanisms underlying hypoxia-induced glioblastoma cell autophagy and indicate that the hypoxia/CREBRF/CREB3/ATG5 pathway plays a central role in malignant glioma progression.

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