应用系统生物学方法研究结直肠癌干细胞分子调控网络及临床意义

项目名称： 应用系统生物学方法研究结直肠癌干细胞分子调控网络及临床意义

项目编号： No.81502705

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 徐怀龙

作者单位： 中国人民解放军第三军医大学

项目金额： 16.5万元

中文摘要： 肿瘤干细胞在肿瘤发生发展、侵袭转移和药物耐受上发挥着重要的作用，但传统的还原论方法并不能有效地从整体水平上阐明其分子调控机制。随着大数据时代的来临，系统生物学逐渐广泛应用于肿瘤分子机制的研究。在本课题中，我们以结直肠癌干细胞为模型，通过系统生物学的方法整合结直肠癌干细胞的多种高通量组学数据，分析模拟反映结直肠癌干细胞的分子框架，预测结直肠癌干细胞的分子调控网络，找出其关键信号通路和潜在药物靶点，并进一步从细胞和动物水平上对其进行功能学方面的验证，同时结合临床样本探讨其临床意义。本项目将为肿瘤干细胞研究提供新的方法借鉴，并为结直肠癌分子机制的深入研究提供新的研究方向。

中文关键词： C08_结；直肠肿瘤；肿瘤系统生物学；肿瘤干细胞；分子调控网络；自我更新

英文摘要： Cancer stem cells (CSCs) play important roles in tumor initiation, development, invasion, metastasis, and drug resistance. However, the molecular regulatory mechanisms of CSCs have been scarcely effectively elucidated at a global level using the traditional reductionist approach. With the advent of the era of big data, systems biology approaches have been widely used to study the molecular mechanisms of cancer. Here, based on a variety of high-throughput omics data of colorectal cancer stem cells, systems biology approaches were used to analyze and simulate their molecular framework, predict their molecular regulatory network, as well as identify their key signaling pathways and potential drug targets. Moreover, We will further validate these data in terms of function at the cellular and animal levels, and explore their clinical significances combined with clinical samples. This study provides insight into the regulatory functions of CSCs for researches, thereby expanding our knowledge of the molecular mechanisms of colorectal cancer.

英文关键词： Colorectal cancer;Cancer systems biology;Cancer stem cells;Molecular regulation network;Self-renewal