急性淋巴细胞白血病预后相关的非编码RNA调控网络和标志物研究

项目名称： 急性淋巴细胞白血病预后相关的非编码RNA调控网络和标志物研究

项目编号： No.31471247

项目类型： 面上项目

立项/批准年度： 2015

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： 成人急性淋巴细胞白血病（ALL）总体预后不好、异质性大且机制不明。基于前期的ALL研究，本项目拟从非编码RNA（ncRNA）调控网络研究成人ALL预后的机制并筛选预后靶标。我们将在已有的miRNA和转录因子（TF）共调控网络研究方法基础上引入长非编码RNA，构建新的TF和ncRNA调控模块并应用于成人ALL预后研究中。首先通过测序鉴定多组不同预后的成人ALL样本（包括初治、缓解、未缓解和复发等）的基因表达，获得不同预后样本组特异表达的基因和ncRNA。然后分别构建不同预后样本中特异的TF和ncRNA调控模块和网络。综合分析并筛选网络中的关键调控因子和模块，探讨其在预后中的作用机制。最后验证调控因子和模块对靶基因及对细胞增殖、迁移等的影响，并在临床样本中检测其与预后的相关性及作为预后标志物的可行性。本项目为提高成人ALL预后效果奠定基础，具有重要的应用价值和学术意义。

中文关键词： 生物信息；非编码RNA；急性淋巴细胞白血病；数据整合；调控网络

英文摘要： Adult acute lymphoblastic leukemia (ALL) is a common type of leukemia with bad and different prognoses, of which the mechanism is unclear. Based on our previous work in ALL, we plan to study the mechanism of adult ALL prognosis from the non-coding RNA (ncRNA) regulatory network, and try to find some marker molecules for prognosis. We will introduce the long non-coding RNA (lncRNA) into our previous constructed transcription factor (TF) and miRNA co-regulatory network. Thus we will construct new TF and ncRNA regulatory modules and apply them into ALL prognosis related network analysis. In this study, we will use high-throughput sequencing technology to detect the expression of coding genes and ncRNAs in multiple groups of ALL samples with different prognosis, which includes samples of untreatment, complete remission, non-remission, and recurrence. Then the specifically expressed genes and ncRNAs will be identified for the good and bad prognosis samples, respectively. And further the TF and ncRNA regulatory modules and networks for both good and bad prognosis ALL samples will be constructed. We will analyze the networks to find some key regulatory factors and modules, and discuss their roles in ALL prognosis. Finally, we will perform experiments to validate the targets in the regulatory modules and their effects in cell proliferation and migration etc. We will also detect the expression of these key genes in much more clinical samples to test their prognosis performance and discuss their potentialities as prognosis markers. This study will provide clues for the adult ALL risk stratification and improvement of the curative effect. It has potential application value and significance on disease study.

英文关键词： Bioinformatics;non-coding RNA;acute lymphoblastic leukemia;data integration;regulatory network