项目名称： 基于基因调控网络的心肌梗死相关分子协同调控模式的研究

项目编号： No.31500675

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 石洪波

作者单位： 哈尔滨医科大学

项目金额： 20万元

中文摘要： 心肌梗死是冠心病最严重的类型之一，是受多因素影响的复杂疾病，因其高发病率和死亡率，为患者和社会带来严重的心理负担和经济负担。对于其分子机制的研究尽管较多，但主要集中于单基因水平。本项目在前期研究工作基础上，首先大规模整合心肌梗死相关分子表达谱及多种分子间的调控互作信息，系统构建全基因组水平包括mRNA、miRNA、转录因子、lncRNA在内的心肌梗死基因调控网络及动态基因调控网络。其次挖掘心肌梗死中核心调控子及协同调控模块，构建多种分子协同调控的通路模型，系统分析心肌梗死相关分子协同调控的潜在机制及其调控的动态性，同时识别心肌梗死多基因联合诊断及预后的标记。最后，运用生物学实验对潜在的诊断及预后标记进行证实。本课题的完成将为深入理解心肌梗死发生发展的分子机制提供新的视角，为心肌梗死患者进行早期诊断、预后评估、靶向治疗提供理论基础和实验依据。

中文关键词： 转录调控网络；功能模块；微小RNA；长链非编码RNA；协同调控

英文摘要： Myocardial infarction is one of the most serious types of coronary heart disease, which is a complex disease that affected by multiple factors. Myocardial infarction brings serious psychological and economic burdens for patients and society because of its higher mortality and morbidity. Although there are many studies on the molecular mechanism of myocardial infarction, most of them are focused on a single gene level. Based on the previous studies, the project will integrate molecular expression profiles and the regulatory relationships among molecules that associated with myocardial infarction on a large scale. We aim to systematically construct a gene regulatory network and a dynamic gene regulatory network for myocardial infarction on the genome-wide scale, and the gene regulatory networks include four types of nodes including mRNA, miRNA, transcription factor and lncRNA. Then, we will identify the regulators and synergistic regulatory modules that might play important roles in myocardial infarction, and build the pathway model for synergistic regulatory molecules. In this way, we systematically analyze the potential synergistic regulatory mechanisms and the regulatory dynamics underlying myocardial infarction. At the same time, we will identify some diagnostic and prognostic markers for myocardial infarction that combined with multiple genes. Finally, we will confirm the results by applying biological experiments to the diagnostic and prognostic markers. The completion of the project will bring new perspectives for further understanding the regulation mechanisms of myocardial infarction, and provide theoretical and experiment basis for early diagnosis, prognosis and targeted therapy.

英文关键词： transcriptional regulatory networks;functional modules;miRNA;long non-coding RNA;synergistic regulation