MicroRNA网络生物学：协同得分定量评估人体MicroRNA协同相互作用

项目名称： MicroRNA网络生物学：协同得分定量评估人体MicroRNA协同相互作用

项目编号： No.31301095

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 朱文良

作者单位： 哈尔滨医科大学

项目金额： 20万元

中文摘要： 现已探明人体中表达超过2000 种miRNA。虽然研究证实单一miRNA可调控多个基因表达而发挥生理病理作用，但对于miRNA之间是否存在内在功能联系还不清楚。揭示人体miRNA相互作用的本质和规模，尤其是发现具有协同治疗效果的miRNA组合，可更好地将此类内源性物质用于重大疾病的预防和治疗。通过创建协同得分这一定量评价参数，我们在前期研究中发现和证实miR-1和miR-21存在显著抗心肌凋亡协同作用，强烈提示此组合可用于心肌缺血相关疾病的治疗。基于以下事实即存在大量miRNA参与细胞凋亡以及细胞凋亡在许多重大疾病病理发展中发挥关键作用，本研究将依据药物协同中效理论，从细胞凋亡角度出发，对协同得分的定量评价性能进行进一步地生物学实验确证，网络生物学揭示miRNA发生协同作用的一般规律，以及发现和证实其它存在显著细胞凋亡协同作用的miRNA组合。研究结果有望为miRNA联合治疗提供理论指导。

中文关键词： miRNA；协同得分；网络生物学；生物标记物；人体复杂疾病

英文摘要： It has been proven that there are more than 2000 miRNAs being expressed in human genome. Although studies have confirmed that single miRNA play physiological and pathological role via regulating the expression of multiple mRNA genes, the inherent functional interactions between different miRNAs is still unclear. Revealling of the nature and scale of human miRNA-miRNA interactions and especially discovery of potential miRNA combinations with synergisitic theray effect has implications for better apllications of such endogenous substances for the prevention and treatment of major diseases. Innovative establishment of a quantitative assessment parameter synergy score prompted us find and evaluate the significant synergistic effect of miR-1 and miR-21 on anti-mycardial-apoptosis. This result strongly suggests that this miRNA combination can be applied for the treatment of myocardial ischemia and the related human diseases. Based on the fact that a large number of miRNAs are implicated in celluar apoptosis and cellular apoptosis plays vital roles in the development of many major disease pathology, this study will further experimentally evaluate the quantitative assesement performance of synergy score in potent miRNA synergy using the median effect drug synergy theory from the cellular apoptosis perspective, reveal th

英文关键词： miRNA；synergy score；network biologgy；biomarker；complex human disease