长链非编码RNA lncAC1调控膀胱癌干细胞自我更新的分子机制研究

项目名称： 长链非编码RNA lncAC1调控膀胱癌干细胞自我更新的分子机制研究

项目编号： No.81472413

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 李翀

作者单位： 中国科学院生物物理研究所

项目金额： 78万元

中文摘要： 发掘新型肿瘤标志物作为诊断与治疗的靶点一直是膀胱癌研究的热点。长链非编码RNA（lncRNA）是近来新发现的一类具有调控基因表达功能的非编码RNA。LncRNA在生命活动及肿瘤发病中具有重要调节作用，但lncRNA对肿瘤干细胞的自我更新的维持知之甚少。我们前期成功分离了膀胱癌干细胞（BCSCs）,通过 RNA表达谱差异分析，鉴定了一批与BCSCs干性密切相关的lncRNA。其中， lncAC1能够显著促进BCSCs的自我更新，增强BCSCs对顺铂等化疗药物的耐受性。我们还发现lncAC1能够上调BRE蛋白的表达，BRE的表达与BCSCs的干性相关。在此基础上，我们将探究lncAC1调控BRE表达的分子机制，揭示lncAC1调控BCSCs干性维持的分子机理，从而明确lncAC1作为膀胱癌干细胞干预新靶点的临床意义，为膀胱癌的临床治疗和药物研发提供理论基础。

中文关键词： C13_膀胱肿瘤；肿瘤干细胞；长链非编码RNA

英文摘要： Bladder cancer is still a major epidemiological problem whose incidence continues to rise each year. Increasing evidence showed tumorigenesis of bladder cancer contributes to alterations in molecular pathways that modulate cellular homeostasis. Major cellular processes are comprised of five intrinsic processes that respond to external carcinogenic signals or become internally deregulated owing to genetic changes, including cell cycle regulation, cell death, cell growth, signal transduction and gene regulation. Tumor maintenance and progression also depend on two extrinsic processes that interact with stromal elements and adjoining cells, harboring angiogenesis and tumor cell invasion. Cancer stem cell (CSC) and long non-coding RNA (lncRNA) are the current research fields for bladder cancer. CSC and lncRNA research in bladder cancer can not only reveal the mechanisms of tumorigenesis, but also provide a new type of candidate marker for cancer diagnosis, therapy and molecular typing. In our project, we expect to find a lncRNA as a novel tumor marker of bladder cancer stem cells and to explore the effect of the lncRNA in bladder cancer tumorigenesis, including biological characteristics of bladder cancer stem cells, single cell exons and transcriptome sequencing, and establishing bladder cancer stem cell lncRNA database. Next, we want to confirm lncAC1 and its interacting protein BRE positions in bladder cancer stem cells, and to prove that lncAC1 can promote tumorigenesis, tumor invasion and drug resistance. Last, we also want to clarify signaling pathways of stemness maintenance by lncAC1 mediated in bladder cancer stem cells and evaluate lncAC1 as a potential therapeutic target used to guide clinical intervention on bladder cancer.

英文关键词： bladder cancer;cancer stem cell;long non-coding RNA