首页|MAGED4B Promotes Glioma Progression via Inactivation of the TNF-α-induced Apoptotic Pathway by Down-regulating TRIM27 Expression

MAGED4B Promotes Glioma Progression via Inactivation of the TNF-α-induced Apoptotic Pathway by Down-regulating TRIM27 Expression

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MAGED4B belongs to the melanoma-associated antigen family;originally found in melanoma,it is expressed in various types of cancer,and is especially enriched in glioblastoma.However,the functional role and molecular mechanisms of MAGED4B in glioma are still unclear.In this study,we found that the MAGED4B level was higher in glioma tissue than that in non-cancer tissue,and the level was positively correlated with glioma grade,tumor diameter,Ki-67 level,and patient age.The patients with higher levels had a worse prognosis than those with lower MAGED4B levels.In glioma cells,MAGED4B overexpression promoted proliferation,invasion,and migration,as well as decreas-ing apoptosis and the chemosensitivity to cisplatin and temozolomide.On the contrary,MAGED4B knockdown in glioma cells inhibited proliferation,invasion,and migration,as well as increasing apoptosis and the chemosensitivity to cisplatin and temozolomide.MAGED4B knockdown also inhibited the growth of gliomas implanted into the rat brain.The interaction between MAGED4B and tripartite motif-containing 27(TRIM27)in glioma cells was detected by co-immunoprecipitation assay,which showed that MAGED4B was co-localized with TRIM27.In addition,MAGED4B overexpression down-regulated the TRIM27 protein level,and this was blocked by carbobenzoxyl-L-leucyl-L-leucyl-L-leucine(MG132),an inhibitor of the proteasome.On the contrary,MAGED4B knockdown up-regulated the TRIM27 level.Furthermore,MAGED4B overexpression increased TRIM27 ubiquitination in the presence of MG132.Accord-ingly,MAGED4B down-regulated the protein levels of genes downstream of ubiquitin-specific protease 7(USP7)involved in the tumor necrosis factor-alpha(TNF-α)-induced apoptotic pathway.These findings indicate that MAGED4B promotes glioma growth via a TRIM27/USP7/receptor-inter-acting serine/threonine-protein kinase 1(RIPl)-dependent TNF-α-induced apoptotic pathway,which suggests that MAGED4B is a potential target for glioma diagnosis and treatment.

GliomaMAGE family member D4BTripartite motif-containing 27Apoptosis

Can Liu、Jun Liu、Juntang Shao、Cheng Huang、Xingliang Dai、Yujun Shen、Weishu Hou、Yuxian Shen、Yongqiang Yu

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Department of Radiology,The First Affiliated Hospital of Anhui Medical University,Hefei 230022,China

Biopharmaceutical Research Institute,Anhui Medical University,Hefei 230032,China

School of Basic Medical Sciences,Anhui MedicalUniversity,Hefei 230032,China

Department of Pathology,The First Affiliated Hospital of Anhui Medical University,Hefei 230022,China

Department of Neurosurgery,The First Affiliated Hospital of Anhui Medical University,Hefei 230022,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of China

8180167981571308

2023

神经科学通报(英文版)
中国科学院上海生命科学研究院

神经科学通报(英文版)

CSTPCDCSCD
影响因子:0.741
ISSN:1673-7067
年,卷(期):2023.39(2)
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