长链非编码RNA在肾透明细胞癌中调控钙结合蛋白S100A6基因表达的机制研究

项目名称： 长链非编码RNA在肾透明细胞癌中调控钙结合蛋白S100A6基因表达的机制研究

项目编号： No.81502448

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 吕香君

作者单位： 中国人民解放军总医院

项目金额： 18万元

中文摘要： 透明细胞癌（ccRCC）是肾细胞癌最常见的病理类型，ccRCC对放化疗均不敏感，针对VHL-HIF和mTOR 通路的靶向治疗效果有限。前期研究表明，S100A6高表达在ccRCC的发生发展中发挥重要作用，且mRNA表达量与肿瘤预后呈正相关。为明确S100A6在肾透明细胞癌中表达升高的原因，前期相关实验中对S100A6过表达和敲除的肾癌细胞进行基因芯片检测发现多个显著差异的LncRNA。 基于以上研究背景，结合最新研究发现，提出假设S100A6在ccRCC中高表达可能由于LncRNA调控表达所致。拟通过扩大样本量检测差异LncRNA的表达，以及体外体内实验验证LncRNA与S100A6靶向调控机制，同时分析LncRNA表达量和临床病理、随访数据相关性，为肾透明细胞癌预后分子标志物的筛选提供理论基础，为治疗靶点提供可能的研究方向和实验依据。

中文关键词： 非编码RNA；钙结合蛋白S100A6；肾透明细胞癌

英文摘要： Among all types of renal cancers, the clear cell renal cell carcinoma (ccRCC) is one of the most common pathology subtypes. Clear cell renal cell carcinoma is insensitive to chemotherapy and radiotherapy. Currently, the targeted therapies for the ccRCC are mainly focused on VHL-HIF pathway and mTOR inhibition, however, the efficacy of targeted treatment is also limited. Our previous studies found elevated S100A6 levels in ccRCC tissues, enhanced tumorigenesis and associated with higher grade pathological features and clinical stages in ccRCC patients. The quantitative mRNA expression of S100A6 in the tumor tissues was an independent risk factor and might be used as a prognostic marker for the metastatic risk of ccRCC. In order to reveal the mechanism of the up-regulation of S100A6 in ccRCC, our pre-experiment found some differentially expressed LncRNA genes in the microarray tests of the S100A6 knockdown and overexpression 786-O cells. Together with the previous studies and recently relative literatures results, we propose hypothesis that long noncoding RNA directs and activates the expression of S100A6, and promotes the tumorigenesis and metastasis of ccRCC. We validate these LncRNA levels in ccRCC tissues, test the biological functions of these LncRNAs, and analyze the relations of the LncRNAs levels and the prognosis of the patients. We wish to find the regulation between LncRNA and expression of S100A6, and a potential therapeutic target in ccRCC.

英文关键词： Long noncoding RNA;S100A6;clear cell renal cell carcinoma