调控细胞增殖与死亡的lncRNA的鉴定及其作用机制研究

项目名称： 调控细胞增殖与死亡的lncRNA的鉴定及其作用机制研究

项目编号： No.91440205

项目类型： 重大研究计划

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 庄诗美

作者单位： 中山大学

项目金额： 300万元

中文摘要： 增殖与凋亡是受到严格调控的细胞生命活动。以往有关增殖与凋亡调控机制的研究主要是围绕蛋白展开。长非编码RNA（lncRNA）的数量远多于蛋白分子，但lncRNA的功能及其作用机制研究才刚刚起步，而调控增殖与凋亡的lncRNA更是有待鉴定。我们前期已在有、无p53的细胞以及肝癌组织中筛选到差异表达的lncRNA和mRNA，并通过生物信息学方法构建了lncRNA和mRNA的共表达网络，筛选了一批受p53表达调控的lncRNA，初步确定了可能调控增殖与凋亡的lncRNA。以此为基础，本项目拟结合体内外模型鉴定：1）目标lncRNA对细胞增殖与凋亡的调控作用；2）目标lncRNA调控细胞增殖与凋亡的分子机制；3）调控目标lncRNA表达的分子机制。研究结果将阐明lncRNA的生物学功能和调控网络，揭示调控细胞增殖与凋亡的新机制，并为发现新的功能分子元件及由其引发的新的生命活动规律提供关键信息。

中文关键词： 非编码RNA；长非编码RNA；细胞增殖；细胞凋亡

英文摘要： Cell proliferation and apoptosis are tightly regulated biological processes. Studies on the regulatory mechanisms of cell proliferation and apoptosis have long been focused on protein coding genes. Although the number of long non-coding RNAs (lncRNAs) is much more than that of proteins, yet our understanding about the biological function and its underlying mechanism of lncRNAs is still very limited. The lncRNAs that regulate cell proliferation and apoptosis remains largely unknown. Based on microarray and bioinformatic analyses, we have identified a cohort of differential expressed lncRNAs and mRNAs, and built the gene co-expression networks, which suggest a group of candidate lncRNAs that may regulate proliferation and apoptosis. With these findings, we will further investigate: 1) the regulatory roles of candidate lncRNAs in cell proliferation and apoptosis; 2) the regulatory mechanisms of candidate lncRNAs; 3) the molecular mechanisms underlying the expression of candidate lncRNAs. The results obtained will not only reveal the biological function and regulatory networks of lncRNA, but also disclose the novel mechanisms responsibe for cell proliferation and apoptosis.

英文关键词： non-coding RNA;long non-coding RNA;proliferation;apoptosis