长链非编码RNA调控胶质瘤血管生成，侵袭，耐药和癌干细胞特性的研究

项目名称： 长链非编码RNA调控胶质瘤血管生成，侵袭，耐药和癌干细胞特性的研究

项目编号： No.81472366

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： 夏洪平

作者单位： 皖南医学院

项目金额： 68万元

中文摘要： 血管生成，侵袭，耐药和癌干细胞特性是导致恶性胶质瘤术后复发与预后差主要因素，寻找调控这些因素关键分子对胶质瘤临床干预有重要意义。我们通过从胶质瘤组织和细胞系中获取胶质瘤干细胞（GSCs），已发现了一些GSCs相关miRNAs表达异常（如miR-124 and miR-218等）。近期预实验又发现一些长链非编码RNAs（lncRNAs）在GSCs中亦显著差异表达（如H19，X，Y，Z等），上调H19促进胶质瘤细胞侵袭，血管生成和神经球形成。本项目将收集胶质瘤病人组织与血液样品，检测GSCs相关lncRNAs表达差异，结合临床分析其作为诊断标志物的应用前景；进一步通过体外细胞与体内动物模型上调或下调lncRNAs表达，结合基因组学与蛋白组学等技术，探究lncRNAs调控胶质瘤血管生成，侵袭，耐药和癌干细胞特性的作用及其分子机制。本研究将为胶质瘤分子诊断与靶向治疗提供新型分子标志物和干预靶点。

中文关键词： C15_脑；中枢神经系统肿瘤；长链非编码RNA；血管生成；耐药；胶质瘤干细胞

英文摘要： Angiogenesis, invasion, drug resistance and stemnnes characteristics of glioma are major factors leading recurrence and poor prognosis of malignant glioma. So it is important on clinical implications to investigate the key molecules on regulation of glioma angiogenesis, invasion, drug resistance and stemnnes for the development of effective molecular markers and therapeutic targets. Our group have isolated glioma stem cells (GSCs) from glioma cell lines and tissues, and identified some GSCs associated microRNAs (eg miR-124 and miR-218, etc.). Recent our preliminary data showed that some long non-coding RNAs (lncRNAs) are significantly different expression in GSCs (such as H19, X, Y, Z , etc. ). This grant application will collect clinical glioma tissues and blood samples of patients to detect differences in the expression of GSCs associated lncRNAs. In combination with clinical analysis, we will investigate the prospects of these lncRNAs as the diagnostic markers of glioma. We will further investigate the effects of these lncRNAs on glioma angiogenesis, invasion, drug resistance and stemnnes characteristics by transient or stable overexpression or knockdown. The molecular mechanisms of these lncRNAs regulation on glioma angiogenesis, invasion, drug resistance and stemnnes properties will be further investigated by genomics and proteomics technologies. This study will provide new molecular markers and intervention targets glioma molecular diagnostics and targeted therapy.

英文关键词： Glioma;Long noncoding RNA;Angiogenesis;Drug resistance;glioma stem cell