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。
Abstract: 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.