miRNA在化学致癌过程中的功能性研究

项目名称： miRNA在化学致癌过程中的功能性研究

项目编号： No.30800930

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 王庆

作者单位： 中山大学

项目金额： 20万元

中文摘要： miRNA是表观遗传的重要表现方式，与肿瘤的发生发展密切相关。为了明确miRNA在化学致癌过程中的功能，本课题拟选择几种环境中常见的化学致癌物作用于人永生化细胞,利用基因芯片技术研究miRNA在化学致癌物诱导的细胞转变不同阶段的表达水平及变化规律，利用生物信息学法和计算机RNA组学法分析细胞转化不同阶段表达差异的miRNA,并通过对其下游靶点的预测筛选出2－3个与化学致癌密切相关的miRNA作为候选基因，在细胞转化模型中上调或下调其表达，研究其在化学物诱癌过程中的作用，并观察其对细胞损伤和修复过程的影响以及在细胞转化过程中与其他表观调控模式的关系，最后采用人群肿瘤分子流行病学的方法对候选miRNA进行验证。本研究将揭示miRNA在化学致癌过程中的功能作用，为肿瘤的化学预防提供新的靶点，并从基因的遗传变异及表观遗传变异两个角度来探讨miRNA在化学致癌过程中的分子机制。

中文关键词： 微小RNA；表观遗传；细胞转化；化学致癌物

英文摘要： MiRNA is an important one of epigenetic regulations, and its abbrevant expression has been closely correlated with human cancer development. In order to elucidate the function of miRNA in the process of chemical carcinogenesis, we will choose several canonical environmental chemical carcinogens to induce the malignant tarnsformation of human immortalized cells, then,we will use microarray technology to investigate the dynamic expression of miRNA profiles in the different stages of the process of human cells transformation. after analyzing predicted downstream targets of those different miRNAs in different stages of the cells transformation by the bioinformatics and computeromics, we will pick up 2-3 potential miRNAs as the candidate targets invloved in chemical carcinogenesis. subsequently, to study their roles in cell transformation, we will upregulate or downregulate these miRNAs in cell models to observe their influences on the DNA damage-repair process, chemical carcinogensis process and other epigenetic reguation models.finally, the expression and function of these candidate miRNAs will be further confirmed in vivo through the population molecular epidemiology.This study will reveal the function of miRNAs in chemical carcinogenesis process and provide a new target for cancer chemoprevention, and elucidate the molecular mechanism of miRNAs in chemical carcinogenesis process from the angles of genetic variation and epigenetic variation.

英文关键词： microRNA; epigenetics; cell transformation; chemical carcinogens