Identification of genes related to nasopharyngeal carcinoma with the help of pathway-based networks
Identification of genes related to nasopharyngeal carcinoma with the help of pathway-based networks
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DOI：
10.1111/j.1745-7270.2006.00235.x
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发表时间：
2006-12-01
影响因子：
3.7
通讯作者：
Yao, Kai-Tai
中科院分区：
文献类型：
--
作者：
Li, Hui;Ren, Cai-Ping;Yao, Kai-Tai
cDNA微阵列是一种同时分析数万个基因表达水平的有力工具。基因芯片检测结果显示，与正常鼻咽组织相比，鼻咽癌组织中有2210个基因存在高度差异表达。由于信号通路被广泛用于描述基因之间的复杂关系，因此本文构建了一个基于通路的网络来可视化从微阵列数据中获得的基因之间的连接。我们对可能对该基因网络有重要影响的靶基因进行了统计分析，发现一些基因可能对该基因网络有重要影响，特别是Ras相关核蛋白（RAN）、羧基酯脂肪酶（CEL）、v-rel网状内皮组织增生症病毒癌基因同源物A（RELA）基因。为了验证基于路径选择的结果，我们采用逆转录-聚合酶链反应（RT-PCR）和实时荧光定量RT-PCR检测RAN、CEL和RELA基因的表达水平，发现RAN和CEL基因在80%以上的NPC组织中显著上调。为了进一步阐明RAN基因的功能，通过RNA干扰（RNAi）在5- 8 F NPC细胞系中特异性抑制RAN表达。正如预期的那样，RAN的耗尽可以有效地阻断肿瘤细胞的增殖。因此，我们的研究可能为分析海量的微阵列数据开辟一条新的途径。
cDNA microarray is a powerful tool to analyze simultaneously the expression levels of tens of thousands of genes. Compared with normal nasopharynx (NP) tissues, 2210 genes were highly differentially expressed in nasopharyngeal carcinoma (NPC) tissues detected by cDNA microarray. Since signal pathway is widely used to describe the complex relationship between genes, a pathway-based network was constructed to visualize the connection between the genes obtained from microarray data in this report. We analyzed the targeted genes that may have more important influence on this gene network with statistical methods and found that some genes might have significant influence on this network, especially Ras-related nuclear protein (RAN), carboxyl ester lipase (CEL), v-rel reticuloendotheliosis viral oncogene homolog A (RELA) genes. To verify the results from pathway-based selection, reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR were performed to detect the expression levels of RAN, CEL and RELA genes and it was found that the RAN and CEL genes were significantly up-regulated in more than 80% of NPC tissues. To further elucidate the function of the RAN gene, RAN expression was specifically suppressed in a 5-8F NPC cell line by RNA interference (RNAi). As expected, the depletion of RAN could effectively block the proliferation of tumor cells. Therefore, our study may open up a new way to analyze the vast microarray data.