新型的以eEF2激酶-调控自噬信号通路为靶点的抗肿瘤药物网络分析  

Network Analysis of Novel Antitumor Drug Targeting eEF2 Kinase Regulating Autophagy Signaling Pathway

作　　者：柳欢[1] 张珂[2] 王航宇[2] 钟益宁[1] 

机构地区：[1]广西中医药大学,广西南宁530299 [2]石河子大学药学院,新疆石河子832002

出　　处：《中国现代中药》2017年第3期346-353,共8页Modern Chinese Medicine

基　　金：广西科技攻关计划项目(桂科重1298001-2-7;桂科攻1346008-4);广西自然基金(2014GXNSFAA118271);2014年博士研究生教育发展项目(050140002)

摘　　要：目的:eEF-2激酶有可能是哺乳动物大自噬的重要组分,研究寻求在电脑中识别以eEF-2K调控的细胞自噬途径为靶点的新的抗肿瘤药物。方法:使用一系列的生物信息学方法和实验步骤,如网络构造(network construction)、枢纽蛋白识别(hub protein identification)、微阵列芯片分析(microarray analyses)、靶向microRNA预测(targeted microRNA prediction)和分子锚定(molecular docking),确定新抗肿瘤药物。结果:通过几个在线数据库的数据,并进一步将它们修饰进入基础的eEF-2K相关联蛋白质之间的反应网络,利用电脑构建了一个全球人类网络工作。以自噬基因的不同表达为基础,确定了eEF-2K调控的自噬中的枢纽蛋白。随后,确认了miRNA能够以eEF-2K调控的自噬为靶向。最后,在Drug Bank和ZINC数据库中扫描了一系列能够在乳腺瘤细胞中以eEF-2K为靶点的分子合成物。结论:系统地确认了以eEF-2K为靶点的新的小分子产物,并预测了靶点抗肿瘤药物。这些发现可能为揭示eEF-2K和自噬之间的复杂关系、并为发现可能的肿瘤药物提供了进一步的线索。Objective： EEF-2 kinase is likely to be important component of large mammals autophagy, seek recognition in computer with eEF-2 k regulation of cell autophagy pathway for targets of new antitumor drugs. EEF-2 kinase is likely to be an important component of mammalian autophagy, and a new anti-tumor drug targeting the eEF-2 kinase signaling pathway may solve this problem. Methods： A series of biological information method and several experiment steps such as network construction, hub protein identification, microarray analyses, targeted microRNA prediction and molecular docking were applied for the determination of new antitumor drugs. Results ： The data form several online database were modified into the basis of the eEF-2K associated protein interaction network and a global network of human work was built by authors. Based on the different expression of autophagy genes, the key protein of eEF-2K regulating autophagy was determined. Subsequently, it was confirmed that miRNA was able to target the autophagy of eEF-2K. Finally, in the DrugBank and ZINC databases, a series of molecular compounds that can targeted at eEF-2K in breast tumor cells were scanned. Conclusion： the new small molecule product with eEF-2K as the target was confirmed, and the antitumor drugs were predicted. These findings may provide further clues to reveal a complex relationship between eEF-2K and autophagy and discovery the possible cancer drugs.

关 键 词：eEF-2K 细胞自噬 肿瘤 AKT 

分 类 号：R979.1[医药卫生—药品]