驱动结直肠癌转移的关键基因甲基化的机制研究

项目名称： 驱动结直肠癌转移的关键基因甲基化的机制研究

项目编号： No.81472252

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： 黄文林

作者单位： 中山大学

项目金额： 85万元

中文摘要： 结直肠癌的转移预后较差。深入研究结直肠癌转移的分子机制对于早期诊断及治疗具有重要意义。基因组中甲基化水平异常是促进结直肠癌进展和转移的重要因素。甲基化水平异常是由关键开关分子参与并调控的。DNA甲基转移酶DNMT1就是开关分子之一。研究证明在结直肠癌中DNMT1活性升高，促使相关抑癌基因的启动子区甲基化而表达沉默，从而促进结直肠癌的转移。本项目拟从DNMT1介导的基因组甲基化水平异常入手，利用芯片筛选由甲基化异常引发的功能基因及miRNA的表达谱变化，得到全景信息。继而以重要候选基因为切入点，研究其在直结肠癌进展和转移中所扮演的角色，得到特异性信息。然后再回到候选基因的甲基化研究，并在临床大样本中评价候选基因的功能及甲基化改变与结直肠癌进展和转移的关系。本课题的顺利实施，有利于阐明甲基化改变促进直结肠癌进展及转移的分子机制，有望为结直肠癌的早期诊断及个体化治疗提供科学依据。

中文关键词： C08_结；直肠肿瘤；DNA甲基化；肿瘤转移

英文摘要： The incidence of colorectal cancer (CRC) in China is currently keeping on increasing. During the clinical treatment against cancer, the patients of phase III or IV often present to be a poor prognosis due to lymph node or distant metastasis. Even the patients, who are all in the stage of phase II, always come with this event within a different prognosis. It is very important to study the molecular mechanism of metastasis of colorectal cancer in sophisticated manner, to explore and discover the early molecules and colorectal cancer metastatic bio-markers for the precise diagnosis and individualized medication. The increased expression of DNA methyltransferase 1 (DNMT1) have been identified that could promote colorectal cancer metastasis which was caused by the abnormal regulation of miR-342. Further investigation revealed that certain metastasis-associated tumor suppressor genes are silenced due to promoter region of the hypermethylation. Therefore, we hypothesis that abnormal genome methylation level is an important biological phenomena for colorectal cancer progression and metastasis which is regulated by the key switch molecules or genes. This project intends to focus on the methylation and metabolism of colorectal cancer progression and metastasis-associated genes by sophisticated research on the metastasis-associated genes methylation levels, how and when non-coding RNA (ncRNA) participate in the regulation with advanced molecular biology techniques. We expect to explore the important molecular markers' life cycles in the colorectal cancer metastatic process and find feasible group of molecular markers for early diagnosis of the colorectal carcinoma, as well as personalized treatment of colorectal cancer as a scientific experimental evidence.

英文关键词： colorectal carcinoma;DNA methylation;tumor metastasis