肺癌组织小RNA修饰的特征分析及调控机制研究

项目名称： 肺癌组织小RNA修饰的特征分析及调控机制研究

项目编号： No.81472181

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： 闫孟红

作者单位： 同济大学

项目金额： 75万元

中文摘要： 肺癌是一种常见的恶性肿瘤疾病，其发病率逐年上升，严重威胁着人类健康。修饰核苷与人类的多种疾病具有非常密切的关系。近年来，DNA甲基化和组蛋白修饰备受人们的关注，而RNA修饰的研究相对非常缺乏，特别是microRNA的修饰。在前期研究中，我们成功的建立了一种基于LC-MS/MS的同时检测多种修饰核苷的方法，并发现小RNA中存在一系列的修饰。本项目重点研究肺癌组织中小RNA的修饰状况；研究异常表达的特定3-5种microRNA的修饰状况及其修饰核苷的定位；探讨RNA修饰对肺癌发生、细胞增殖、转移的作用及机制。本项目的研究将为microRNA修饰的研究奠定良好的基础，将有助于阐明microRNA的结构和功能，具有较强的创新性；将对肺癌发病机制的研究提供可靠的理论和实验依据，为肺癌等疾病的诊治提供新的思路。

中文关键词： C05_气管；支气管；肺肿瘤；小RNA；修饰核苷；质谱分析；基因表达

英文摘要： Lung cancer is a common malignant disease which threatens human health seriously. Its incidence and mortality rate increased dramatically year by year. Many diseases had been found to be associated with a large number of modified nucleotides. Methylation of DNA and histone modification has attracted a widely concern in recent years, while little is known about modification of small RNA, even less is known about the function of the modifications in microRNA. Based on previous work, we have established a method successfully to detect a variety of modified nucleosides at the same time by liquid chromatography-mass spectrometry (LC-MS/MS) and found there are a variety of modified nucleosides in small RNA. This project focuses on analysis of small RNA modification in lung cancer tissue by LC-MS/MS. We will also investigate on the modification of specific single microRNAs that expressed abnormally in lung cancer and the position of modified nucleosides in a single microRNA. Moreover, we will study the function and mechanism of modified nucleotides in small RNAs from lung cancer tissue. This project will provide a good foundation on microRNA modification and it may be helpful to investigate on the structure and function of microRNAs. It will provide reliable theoretical and experimental data for explaination the pathogenesis of lung cancer and give a new idea to cancer therapy.

英文关键词： lung cancer;small RNA;modified nuleosides;mass spectrometry;gene expression