Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells.
Sox2, a master transcription factor, contributes to the generation of induced pluripotent stem cells and plays significant roles in sustaining the self-renewal of neural stem cells and glioma-initiating cells. Understanding the functional differences of Sox2 between glioma-initiating cells and normal neural stem cells would contribute to therapeutic approach for treatment of brain tumors. Here, we first demonstrated that Sox2 could contribute to the self-renewal and proliferation of glioma-initiating cells. The following experiments showed that Sox2 was activated at translational level in a subset of human glioma-initiating cells compared with the normal neural stem cells. Further investigation revealed there was a positive correlation between Sox2 and eukaryotic initiation factor 4E (eIF4E) in glioma tissues. Down-regulation of eIF4E decreased Sox2 protein level without altering its mRNA level in glioma-initiating cells, indicating that Sox2 was activated by eIF4E at translational level. Furthermore, eIF4E was presumed to regulate the expression of Sox2 by its 5' untranslated region (5' UTR) sequence. Our results suggest that the eIF4E-Sox2 axis is a novel mechanism of unregulated self-renewal of glioma-initiating cells, providing a potential therapeutic target for glioma.
Ge
Yuqing
Y
Key Laboratory of Glycoconjuates Research, Ministry of Public Health & Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032, China.
Zhou
Fengbiao
F
Chen
Hong
H
Cui
Chunhong
C
Liu
Dan
D
Li
Qiuping
Q
Yang
Zhiyuan
Z
Wu
Guoqiang
G
Sun
Shuhui
S
Gu
Jianxin
J
Wei
Yuanyan
Y
Jiang
Jianhai
J
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D014176:Protein Biosynthesis; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
D039561:Eukaryotic Initiation Factor-4E; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors