用系统生物学方法对miRNAs介导的癌细胞死亡网络的研究

项目名称： 用系统生物学方法对miRNAs介导的癌细胞死亡网络的研究

项目编号： No.U1304311

项目类型： 联合基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 徐建震

作者单位： 河南工业大学

项目金额： 30万元

中文摘要： 癌细胞死亡进程受到包括细胞凋亡和自噬等信号途径的协同调节。采用系统生物学方法分析 miRNAs在癌细胞死亡网络中的分子机制及全局性作用是具有挑战意义的课题。本研究通过有机整合遗传变异、转录调控、表达谱和蛋白互作谱等各种组学数据，分析调控癌细胞死亡的 miRNAs在调控序列、表达谱关系、靶蛋白互作谱以及靶蛋白功能富集类等多方面的特征，利用KNN、SVM等各种机器学习及数据融合方法设计预测算法，从系统的角度识别新的死亡相关 miRNAs及其差异化功能。借助细胞转染、免疫荧光以及流式细胞检测等生物学实验揭示miRNAs在癌细胞死亡进程重要作用。在此基础上，构建包含多层面信息的、miRNAs介导的细胞死亡调控网络,阐明其中调控规律和特征。研究结果将有助于理解凋亡与自噬通路协同调控癌细胞死亡的分子机制，为抗癌治疗提供理论基础。

中文关键词： miRNAs；细胞死亡；miRNA-蛋白互作；数据库；

英文摘要： Mammalian cells have evolved several elegant mechanisms to die, including apoptosis and autophagy. These two signaling pathways can coordinately modulate the cell death process in cancers. In recent years, substantial research interests have arisen to decipher miRNA function in cell death pathways. Previously we also showed that enforced expression of MIR153 increases apoptosis via targeting B-cell lymphoma 2 (BCL2),myeloid cell leukemia sequence 1 (MCL1) and insulin receptor substrate-2 (IRS2),linking this tumor suppressor to the apoptosis pathway. Despite enormous success, it is increasingly evident that systems biology approaches are essential to uncover the generic organizing principles of the miRNA mediated cell death network.For the first step toward understanding the network architecture, we have developed miRDeathDB (http://rna-world.org/mirdeathdb/), a knowledge depository that integrates information for experimentally identified miRNAs and their targets in cell death network.In this project, we propose to integrate a variety of omics data centering on cell death related miRNAs. This information includes SNP data,expression profile for both miRNAs and their targets,transcription factor-miRNAs data,protein-protein interaction data, signaling pathways data and Gene Ontology annotations. Then the charact

英文关键词： miRNAs；cell death；miRNA-protein interaction；database；