去乙酰化酶SIRT1 调控胃癌浸润转移的机制研究

项目名称： 去乙酰化酶SIRT1 调控胃癌浸润转移的机制研究

项目编号： No.81472270

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： 杨青

作者单位： 山东大学

项目金额： 70万元

中文摘要： 浸润转移是肿瘤的重要生物学特征，上皮-间质转化（EMT）在这一恶性进展过程中发挥重要作用。本课题组发现去乙酰化酶SIRT1可通过诱导细胞周期阻滞抑制胃癌的发生，但SIRT1能否调节EMT影响胃癌的浸润转移尚不清楚。我们的初步研究结果显示胃癌组织中SIRT1的表达与肿瘤的分化存在相关性，抑制SIRT1能诱导胃癌细胞形态从上皮向间质转化，增强细胞的迁移能力并调节EMT标志物的表达变化。本课题组拟在前期工作基础上进行以下研究：（1）利用细胞和动物模型通过体外和体内实验检测SIRT1调节EMT在胃癌浸润转移过程中的生物学功能，（2）在分子水平探讨SIRT1调节EMT影响胃癌浸润转移的具体机制，（3）扩大临床标本容量，从组织水平明确SIRT1与EMT及胃癌临床病理学特征间的相关性，从而阐明SIRT1在胃癌浸润转移过程中的作用，为抑制胃癌进展提供新的理论依据和治疗靶点。

中文关键词： C07_胃肿瘤；去乙酰化酶；SIRT1；上皮-间质转化；肿瘤转移

英文摘要： Invasion and metastasis are the main characters of cancer and epithelial-mesenchymal transition (EMT) plays an important role during this process. In the previous work, we found that SIRT1, a histone deacetylase, could inhibit the tumorigenesis of gastric cancer through inducing G1 phase arrest. However, the role of SIRT1 in the invasion and metastasis of gastric cancer has not been well studied. Analysis of our on hand clinic samples suggested that the expression level of SIRT1 was related to the differentiation status of gastric cancer. Our preliminary study on gastric cancer cells showed that inhibition of SIRT1 induced the mesenchymal morphology changes, significantly enhanced the cell motility and regulated the expression levels of EMT markers. In the present project we would go on to study: first, the role of SIRT1 in the invasion and metastasis of gastric cancer through regulation of EMT using in vitro and in vivo experiments; second, explore the molecular mechanism underlying regulation of EMT by SIRT1; third, expand the scale of clinic samples and analyze the relationship between SIRT1 levels and EMT markers as well as the clinical characters of gastric cancer. Our work may clarify the role and the underlying mechanism of SIRT1 in the regulation of invasion and metastasis of gastric cancer and thus provide new targets for inhibiting gastric cancer progression.

英文关键词： gastric cancer;deacetylase;SIRT1;EMT;metastasis