构建以RACK1为核心口腔鳞状细胞癌差异基因间相互作用的关系网路  

Constructing an interaction network of differential genes of oral squamous cell carcinoma with RACK1 as a core

作　　者：郑建伟[1,2] 利小平 董俊英[2] 曾宪丽[2] 梁友龙 韩帮峰 杨德群[2] 罗刚[1] 

机构地区：[1]南方医科大学附属广东省口腔医院,广东省广州市510280 [2]广东省深圳牙科医疗中心,广东省深圳市518001

出　　处：《中国组织工程研究》2015年第18期2911-2916,共6页Chinese Journal of Tissue Engineering Research

基　　金：广东省医学科学研究基金资助项目(A2011092);国家自然科学基金资助项目(81271159/H1405)~~

摘　　要：背景:RACK1与口腔鳞状细胞癌的发生发展密切相关,但肿瘤的发生发展不是一个基因或蛋白决定的,是多基因、多分子呈网络结构,多步骤、多阶段共同作用的长期复杂过程,各肿瘤基因之间相互协同作用促使肿瘤细胞形成和发展。因此要揭示口腔鳞状细胞癌的作用机制将不能局限于单个蛋白或基因,而要着眼于与口腔鳞状细胞癌差异蛋白或基因相关的信号网络通路,研究整个信号通路中相关蛋白或基因的表达变化,进而分析研究这些分子之间的相互作用机制。目的:筛选出的口腔鳞状细胞癌相关差异基因,使用STRING数据库通过生物信息学的方法构建它们之间的相互作用关系网络,为后续实验提供线索。方法:根据作者所在课题组前期口腔鳞状细胞癌的经典蛋白组学实验结果和基因表达谱芯片实验的数据结果,选择表达一致且差异相对较大的基因作为实验的差异基因。将筛选的差异基因输入STRING数据库进行分析,找出差异基因对应蛋白之间的可能作用关系,构建相互作用网络结构图。结果与结论:口腔鳞状细胞癌的19个差异基因对应蛋白相互间构成一个复杂的作用网络,各差异蛋白间通过多条相互作用通路进行调节,RACK1蛋白是整个网络的节点蛋白。GNB2L1的编码蛋白RACK1蛋白通过WD40重复蛋白亚基(编号COG2319)和β-G蛋白亚基(编号KOG0279)与其他差异蛋白的亚基间相互作用。其中WD40重复蛋白(编号COG2319)与其中5个差异蛋白直接作用并构建了10条相互作用通路,β亚基G蛋白(编号KOG0279)与其中8个差异蛋白直接作用并构建了11条相互作用通路。说明通过STRING数据库分析构建了这19个差异基因相互作用的结构网络图发现RACK1蛋白的2个亚基共与8个相关差异蛋白直接作用,产生18条相互作用通路。在这个网络结构中RACK1蛋白是中心,提示其是口腔鳞状细胞癌的一个关键节点蛋白。BACKGROUND：RACK1 is strongly associated with the occurrence and development of oral squamous cel carcinoma. However, the occurrence and development of tumor do not depend on a gene or protein, but a long-term complex process of a network structure of multiple genes and multiple molecules, multi-step, multi-stage joint action. Synergism between tumor genes promotes the formation and development of tumor cel s. Therefore, we cannot limit on a single gene or protein to discover the action mechanism of oral squamous cel carcinoma, but should pay attention on signaling network path related to differential protein or gene, investigate the alterations in related protein or gene expression in the whole signaling pathway, and analyze the action＆nbsp;mechanism of the interaction of these molecules. OBJECTIVE：To screen differential genes related to oral squamous cel carcinoma, construct an interaction network through bioinformatics using STRING database, and provide clues for future tests. METHODS：In accordance with our previous classic proteomics results and microarray results of oral squamous cel carcinoma, genes with consistent expression and big differences were selected as differential genes. The differential genes were inputted into the database of STRING to find the possible relationship among the protein subunits and to construct network structure of their interaction. RESULTS AND CONCLUSION：The 19 differential proteins of oral squamous cel carcinoma construct a complicated net work, and the differential proteins interact through these networks. GNB2L1-encoded RACK1 is a node protein and interacts with other differential proteins via WD40 repeated protein （number COG2319） andβ-G protein subunit （number KOG0279）. WD40 repeated protein （number COG2319） interacts with 5 differential proteins directly and constructs 10 interacting pathways.β-G protein subunit （number KOG0279） interacts with 8 differential proteins directly, which has 11 interacting pathways. We make a network structure pic

关 键 词：实验动物 组织构建实验模型 口腔鳞状细胞癌 差异基因 差异蛋白 RACK1 GNB2L1 STRING数据库 网络调节 作用通路 国家自然科学基金 

分 类 号：R318[医药卫生—生物医学工程]