Transcriptional signaling pathways inversely regulated in Alzheimer's disease and glioblastoma multiform.
Transcriptional signaling pathways inversely regulated in Alzheimer's disease and glioblastoma multiform.
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转录信号通路在阿尔茨海默病和多形性胶质母细胞瘤中受到反向调节。
DOI：
10.1038/srep03467
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发表时间：
2013-12-10
影响因子：
4.6
通讯作者：
Wong ST
中科院分区：
文献类型：
--
作者：
Liu T;Ren D;Zhu X;Yin Z;Jin G;Zhao Z;Robinson D;Li X;Wong K;Cui K;Zhao H;Wong ST
令人信服的流行病学数据表明，癌症和神经退行性疾病（包括阿尔茨海默病（AD））之间存在负相关。由于AD和癌症都以异常但相反的细胞行为为特征，即，AD中细胞死亡增加，而癌症中细胞过度生长，这促使我们开始研究揭示AD和多形性胶质母细胞瘤（GBM）之间的共同基因和细胞信号通路。在这项研究中，对1，091个GBM和524个AD队列的临床微阵列数据集进行了全面的生物信息学分析。从生物信息学分析中鉴定了重要的基因和途径-特别是ERK/MAPK信号传导，在GBM中上调，血管生成素信号传导途径，在AD中上调-连接GBM和AD（P < 0.001），详细研究了它们在AD环境中GBM生长中的作用。我们的研究结果表明，在AD背景下GBM生长的抑制是由ERK-AKT-p21细胞周期途径和抗血管生成途径介导的。
Convincing epidemiological data suggest an inverse association between cancer and neurodegeneration, including Alzheimer's disease (AD). Since both AD and cancer are characterized by abnormal, but opposing cellular behavior, i.e., increased cell death in AD while excessive cell growth occurs in cancer, this motivates us to initiate the study into unraveling the shared genes and cell signaling pathways linking AD and glioblastoma multiform (GBM). In this study, a comprehensive bioinformatics analysis on clinical microarray datasets of 1,091 GBM and 524 AD cohorts was performed. Significant genes and pathways were identified from the bioinformatics analyses – in particular ERK/MAPK signaling, up-regulated in GBM and Angiopoietin Signaling pathway, reciprocally up-regulated in AD – connecting GBM and AD (P < 0.001), were investigated in details for their roles in GBM growth in an AD environment. Our results showed that suppression of GBM growth in an AD background was mediated by the ERK-AKT-p21-cell cycle pathway and anti-angiogenesis pathway.