SMYD3/RIZ信号通路调控食管癌发病的表观遗传学机制研究

项目名称： SMYD3/RIZ信号通路调控食管癌发病的表观遗传学机制研究

项目编号： No.81201945

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 董尚文

作者单位： 天津医科大学

项目金额： 23万元

中文摘要： 前期工作应用基因转染、基因沉默、MSP、免疫印迹等技术发现：SMYD3在食管癌中高表达；RIZ1低表达抑癌活性减低，与DNA启动子甲基化相关；通过沉默SMYD3、逆转甲基化、转染RIZ1的多种手段均使得RIZ1表达上调且抑癌活性恢复，同时伴随有C-myc及VEGF等促肿瘤发病重要靶点的表达水平下降。在此基础上拟通过组蛋白H3K4甲基化定量检测、MSP分析，DZNep、LSD1、5-aza-CdR逆转甲基化等方法研究SMYD3/RIZ通路中SMYD3介导组蛋白甲基化修饰作用于RIZ1的方式与机制及其与DNA启动子甲基化的关系，并通过流式细胞术、SRB、MTT、transwell等研究SMYD3调控RIZ平衡对食管癌细胞生物学行为的影响，为SMYD3/RIZ相关信号通路在食管癌发生发展中的分子机理、为食管癌分子治疗提供理论基础和实验依据，具有重要意义及应用前景。

中文关键词： 食管癌；SMYD3；RIZ1；表观遗传；组蛋白甲基化

英文摘要： In our previous work, several techniques, such as gene transfection, gene silence, MSP, Western Blotting and et al, were applied. We have found that, SMYD3 expressed in a high level in esophageal carcinoma, while RIZ1 was in a low level and its tumor-suppressor activity has diminished. We believe that these phenomena are relevant with methylation, and we have successfully realized the increase of expression level of RIZ1 and the recovery of its tumor-suppressor activity through silencing SMYD3, reversing methylation, transfecting RIZ1 and etc. In the meantime, the expression at C-myc, VEGF and some other important target points which can trigger the tumor has been well lowered down. Accordingly, we plan to study the fashion and mechanism that the SMYD3 mediated histone methylation modification affects the RIZ1 in the SMYD3/RIZ pathway and its relationship with DNA promoter methylation by means of histone H3K4 qualitative methylation detecting, MSP analysis, DZNep, LSD1 and 5-aza-CdR methylation reversion. In addition, the influence of the RIZ balance, which is regulated by SMYD3 on the biological behavior of esophageal carcinoma cells is also within our research extent through flow cytrometry, SRB, MTT, transwell and et al, for we wish to find the molecular mechanism of the signal pathways relevant with SMYD3/RI

英文关键词： Esophageal；SMYD3；RIZ1；Epigenetic；Histone Methylation