儿童和成人急性T淋巴细胞白血病中miRNA和转录因子共调控网络的差异性研究

项目名称： 儿童和成人急性T淋巴细胞白血病中miRNA和转录因子共调控网络的差异性研究

项目编号： No.31270885

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 郭安源

作者单位： 华中科技大学

项目金额： 80万元

中文摘要： 急性T淋巴细胞白血病（T-ALL）严重危害人类健康，其中成人患者的疗效明显差于儿童，且分子机制不明。转录因子（TF）和miRNA 均为重要的基因表达调控因子。基于我们前期成功建立的miRNA和TF在复杂疾病中的共调控网络研究方法，本项目拟研究儿童和成人T-ALL之间的差异调控机制。首先采用高通量测序方法鉴定儿童和成人T-ALL中的差异基因和miRNA，构建差异miRNA和TF共调控前馈环模块及网络，然后分析miRNA相关SNP对该网络的影响。综合分析筛选调控网络中的关键miRNA和模块，探讨其在儿童和成人T-ALL中的差异性作用。最后实验验证调控模块，并在体外和体内验证miRNA对T-ALL细胞增殖、迁移和凋亡等特征的影响及对T-ALL模型小鼠的影响。本项目为揭示儿童和成人T-ALL的疗效差异性提供新的调控机制，为发现潜在的重要靶标和干预手段提供基础，具有重要的应用价值和学术意义。

中文关键词： 急性淋巴细胞白血病；转录因子；miRNA；调控网络；差异表达

英文摘要： T-cell acute lymphoblastic leukemia (T-ALL) is a serious disease damaging human being's health. Adult T-ALL patients have a worse prognosis, with a much lower disease-free survival rates than childhood T-ALL patients and the mechanism of the difference is unknown. Transcription factor (TF) and miRNA are both key regulators of gene expression. We have developed an approach to study their co-regulatory network in complex diseases. In this study, based on our previous work, we proposed to study the different mechanisms of childhood and adult T-ALL based on the miRNA and TF co-regulatory network. Firstly, we will characterize the differential genes and miRNAs between childhood and adult T-ALL patients by high-throughput sequencing. Based on these genes and miRNAs, we will construct the miRNA-TF feed forward loop and co-regulatory network and further analyze the effects of miRNA-related SNPs on this network. Then, we will identify the key regulators and modules in the network and analyze their functions in the childhood and adult T-ALL. Finally, we will perform experiments to confirm the regulatory relationship of the key modules, study the effects of miRNAs on the T-ALL cell proliferation, migration, and the survive of T-ALL mice. This study will provide new insights and regulatory mechanisms in the difference of ch

英文关键词： Acute lymphoblastic leukemia；transcription factor；miRNA；regulatory network；differential expression