SOX4通过Akt-p53轴抑制胶质母细胞瘤细胞生长并诱导G0/G1期细胞周期阻滞。
SOX4 inhibits GBM cell growth and induces G0/G1 cell cycle arrest through Akt-p53 axis.
作者信息
Zhang Jing, Jiang Huawei, Shao Jiaofang, Mao Ruifang, Liu Jie, Ma Yingying, Fang Xuefeng, Zhao Na, Zheng Shu, Lin Biaoyang
机构信息
Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, P R China.
Systems Biology Division and Propriumbio Research Center, Zhejiang-California International Nanosystems Institute (ZCNI), Zhejiang University, Hangzhou, Zhejiang Province, P R China.
出版信息
BMC Neurol. 2014 Nov 1;14:207. doi: 10.1186/s12883-014-0207-y.
BACKGROUND
SOX4 is a transcription factor required for tissue development and differentiation in vertebrates. Overexpression of SOX4 has been reported in many cancers including glioblastoma multiforme (GBM), however, the underlying mechanism of actions has not been studied. In this study, we investigated the role of SOX4 in GBM.
METHODS
Kaplan-Meier analysis was performed to assess the association between SOX4 expression levels and survival times in primary GBM samples. Cre/lox P system was used to generate gain or loss of SOX4 in GBM cells, and microarray analysis uncovered the regulation network of SOX4 in GBM cells.
RESULTS
High SOX4 expression was significantly associated with good prognosis of primary GBMs. SOX4 inhibited the growth of GBM cell line LN229, A172G and U87MG, partly via the activation of p53-p21 signaling and down-regulation of phosphorylated AKT1. Gene expression profiling and subsequent gene ontology analysis showed that SOX4 influenced several key pathways including the Wnt/ beta-catenin and TGF-beta signaling pathways.
CONCLUSIONS
Our study found that SOX4 acts as a tumor suppressor in GBM cells by induce cell cycle arrest and inhibiting cell growth.
背景
SOX4是脊椎动物组织发育和分化所需的一种转录因子。已有报道称SOX4在包括多形性胶质母细胞瘤（GBM）在内的多种癌症中过表达，然而，其潜在作用机制尚未得到研究。在本研究中，我们调查了SOX4在GBM中的作用。
方法
进行Kaplan-Meier分析以评估原发性GBM样本中SOX4表达水平与生存时间之间的关联。使用Cre/lox P系统在GBM细胞中实现SOX4的增减，微阵列分析揭示了GBM细胞中SOX4的调控网络。
结果
SOX4高表达与原发性GBM的良好预后显著相关。SOX4抑制GBM细胞系LN229、A172G和U87MG的生长，部分是通过激活p53-p21信号通路和下调磷酸化AKT1实现的。基因表达谱分析及随后的基因本体分析表明，SOX4影响了包括Wnt/β-连环蛋白和TGF-β信号通路在内的几个关键通路。
结论
我们的研究发现，SOX4通过诱导细胞周期停滞和抑制细胞生长，在GBM细胞中发挥肿瘤抑制作用。
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