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http://dx.doi.org/10.3340/jkns.2021.0298

EID3 Promotes Glioma Cell Proliferation and Survival by Inactivating AMPKα1  

Xiang, Yaoxian (Department of Hand Surgery, Huashan Hospital, Fudan University)
Zhu, Lei (Department of Radiology, Beijing Electric Power Hospital)
He, Zijian (Department of Neurosurgery, Minhang Hospital, Fudan University)
Xu, Lei (Department of Hand Surgery, Huashan Hospital, Fudan University)
Mao, Yuhang (Department of Neurosurgery, Minhang Hospital, Fudan University)
Jiang, Junjian (Department of Hand Surgery, Huashan Hospital, Fudan University)
Xu, Jianguang (Department of Hand Surgery, Huashan Hospital, Fudan University)
Publication Information
Journal of Korean Neurosurgical Society / v.65, no.6, 2022 , pp. 790-800 More about this Journal
Abstract
Objective : EID3 (EP300-interacting inhibitor of differentiation) was identified as a novel member of EID family and plays a pivotal role in colorectal cancer development. However, its role in glioma remained elusive. In current study, we identified EID3 as a novel oncogenic molecule in human glioma and is critical for glioma cell survival, proliferation and invasion. Methods : A total of five patients with glioma were recruited in present study and fresh glioma samples were removed from patients. Four weeks old male non-obese diabetic severe combined immune deficiency (NOD/SCID) mice were used as transplant recipient models. The subcutaneous tumor size was calculated and recorded every week with vernier caliper. EID3 and AMP-activated protein kinase α1 (AMPKα1) expression levels were confirmed by real-time polymerase chain reaction and Western blot assays. Colony formation assays were performed to evaluate cell proliferation. Methyl thiazolyl tetrazolium (MTT) assays were performed for cell viability assessment. Trypan blue staining approach was applied for cell death assessment. Cell Apoptosis DNA ELISA Detection Kit was used for apoptosis assessment. Results : EID3 was preferentially expressed in glioma tissues/cells, while undetectable in astrocytes, neuronal cells, or normal brain tissues. EID3 knocking down significantly hindered glioma cell proliferation and invasion, as well as induced reduction of cell viability, apoptosis and cell death. EID3 knocking down also greatly inhibited tumor growth in SCID mice. Knocking down of AMPKα1 could effectively rescue glioma cells from apoptosis and cell death caused by EID3 absence, indicating that AMPKα1 acted as a key downstream regulator of EID3 and mediated suppression effects caused by EID3 knocking down inhibition. These findings were confirmed in glioma cells generated patient-derived xenograft models. AMPKα1 protein levels were affected by MG132 treatment in glioma, which suggested EID3 might down regulate AMPKα1 through protein degradation. Conclusion : Collectively, our study demonstrated that EID3 promoted glioma cell proliferation and survival by inhibiting AMPKα1 expression. Targeting EID3 might represent a promising strategy for treating glioma.
Keywords
Glioma; EP300-interacting inhibitor of differentiation; AMP activated protein kinase ${\alpha}1$;
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