A20 is overexpressed in glioma cells and may serve as a potential therapeutic target.
OBJECTIVE
A20 is a TNF-inducible primary response gene, which has been found to have antiapoptotic function in several cancer cells. This study investigates A20 expression in human glioma tissues and four glioma cell lines, and its effect on tumorigenesis of glioma cells and a mouse tumor model.


METHODS
Human glioma tissue samples and cells were subject to reverse transcription-PCR (RT-PCR), western blotting and immunohistochemistry. Glioma cells was tested by flow cytometry. A xenograft tumor model in mice was utilized to examine the knock-down effect of specific A20 siRNAs on tumorigenesis.


RESULTS
A20 was overexpressed in clinical glioma tissue samples (63.9%) and correlated with clinical staging. All four human glioma cell lines expressed A20, among which U87 displayed the strongest expression signals. Inhibiting A20 expression by siRNAs in vitro reduced the growth rates of glioma cells and resulted in G1/S arrest and increased apoptosis. In a mouse tumor model, local administration of siRNA significantly suppressed solid tumor growth.


CONCLUSIONS
A20 was overexpressed both in human glioma tissues and cell lines, and inhibiting A20 expression greatly slowed tumor cell growth in culture and in mice. These findings indicated that A20 is involved in tumorigenesis of human glioma, and may serve as a future therapeutic target.
Guo
Qingdong
Q
The Fourth Military Medical University, Xijing Hospital, Department of Neurosurgery, Xi'an 710032, China.
Dong
Hui
H
Liu
Xiaonan
X
Wang
Chunmei
C
Liu
Nannan
N
Zhang
Jianning
J
Li
Bing
B
Cao
Weidong
W
Ding
Tianbing
T
Yang
Zengyue
Z
Zhang
Xiang
X
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins; D016503:Drug Delivery Systems; D005260:Female; D005434:Flow Cytometry; D016193:G1 Phase / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D034741:RNA, Small Interfering / Q000008:administration & dosage; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016196:S Phase / Q000235:genetics; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D023041:Xenograft Model Antitumor Assays
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3