Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells
Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells
复制标题
Sox2 在人胶质瘤起始细胞中被真核起始因子 4E 翻译激活
DOI：
10.1016/j.bbrc.2010.06.015
复制
发表时间：
2010-07-09
影响因子：
3.1
通讯作者：
Jiang, Jianhai
中科院分区：
文献类型：
--
作者：
Ge, Yuqing;Zhou, Fengbiao;Jiang, Jianhai
SOX2是一种主要的转录因子，参与诱导多能干细胞的产生，并在维持神经干细胞和胶质瘤起始细胞的自我更新方面发挥重要作用。了解SOX2在脑胶质瘤起始细胞和正常神经干细胞中的功能差异将有助于脑肿瘤的治疗。在这里，我们首先证明了Sox2可以促进胶质瘤启动细胞的自我更新和增殖。以下实验表明，与正常神经干细胞相比，Sox2在人脑胶质瘤启动细胞亚群中的翻译水平上被激活。进一步研究发现，在脑胶质瘤组织中，Sox2与真核细胞起始因子4E(EIF4E)呈正相关。EIF4E的下调降低了胶质瘤启动细胞中Sox2的蛋白水平，但不改变其mRNA水平，表明eIF4E在翻译水平激活了Sox2。此外，eIF4E可能通过其5‘非翻译区(5’UTR)序列来调控Sox2的表达。我们的结果提示eIF4E-Sox2轴是一种新的无调控的胶质瘤启动细胞自我更新的机制，为胶质瘤的治疗提供了一个潜在的靶点。(C)2010 Elsevier Inc.保留所有权利。
Sox2, a master transcription factor, contributes to the generation of induced pluripotent stern 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. (C) 2010 Elsevier Inc. All rights reserved.