囊泡运输和Ras/MAPK信号转导通路基因甲基化水平与大肠癌发病及预后的关系

项目名称： 囊泡运输和Ras/MAPK信号转导通路基因甲基化水平与大肠癌发病及预后的关系

项目编号： No.81473055

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： 赵亚双

作者单位： 哈尔滨医科大学

项目金额： 80万元

中文摘要： 囊泡运输主要负责胞内物质运输、信号传递等，其运输障碍会导致多种细胞器缺陷和细胞功能紊乱，促进肿瘤发生、侵袭和转移。Ras/MAPK信号转导通路调控细胞增殖与凋亡，与肿瘤密切相关。Ras能调控囊泡转运。由此推测囊泡运输与Ras/MAPK共同调控胞内信号传递，协同促进肿瘤细胞恶性增殖、侵袭和转移。DNA甲基化可影响基因转录导致蛋白质表达异常，诱发肿瘤。囊泡运输相关基因甲基化与大肠癌关系的体内外及人群流行病学研究均未见报道。Ras/MAPK通路癌基因呈现低甲基化，但尚未有其与大肠癌关系的人群流行病学研究。本研究拟采用病例对照研究探索囊泡运输及Ras/MAPK通路基因甲基化、二者的交互作用及二者与环境因素的交互作用和大肠癌发病的关系；采用队列研究探索囊泡运输及Ras/MAPK通路基因甲基化、二者的交互作用及二者与环境因素的交互作用和大肠癌预后的关系；为大肠癌早期预防和个体化治疗提供理论依据。

中文关键词： 囊泡运输；Ras/MAPK信号转导通路；甲基化；大肠癌

英文摘要： Vesicle trafficking is mainly responsible for intracellular macromolecules transport and signal transduction et al. The transport barrier leads to various organelles defects and cell dysfunction, promote tumorigenesis, invasion and metastasis. Ras/MAPK signal transduction pathway regulates cell proliferation and apoptosis, promote tumorigenesis, invasion and metastasis. Ras of the Ras/MAPK pathway could mediate vesicle movement. Therefore, we infer that Vesicle trafficking and Ras/MAPK could jointly regulate intracellular signal transduction; synergistically promote malignant proliferation, invasion and metastasis of tumor cells. DNA methylation could affect gene transcription and lead to abnormal expression of protein, finally induce tumor. Yet no in vivo, in vitro study and epidemiologic study aimed to explore the relationship between the DNA methylation of vesicle trafficking and colorectal cancer. Oncogenes in Ras/MAPK pathway present hypomethylation, but no epidemiologic study aimed to explore the relationship between hypomethylation of Ras/MAPK and colorectal cancer risk and prognosis. Therefore, we carry out a case-control study to explore the associations between DNA methylation of Vesicle trafficking and Ras/MAPK and colorectal cancer risk, their interactions and their interactions with environmental factors on colorectal cancer risk; we then conduct a cohort study to explore the associations between DNA methylation of Vesicle trafficking and Ras/MAPK and colorectal cancer prognosis, their interactions and their interactions with environmental factors on colorectal cancer prognosis; hoping to explore the biomarker panels for early prevention and individualized treatment of colorectal cancer.

英文关键词： vesicle trafficking;Ras/MAPK pathway;methylation;colorectal cancer