SMYD3调控Wnt/β-catenin信号通路的分子机制及其在肝细胞癌中功能的研究

项目名称： SMYD3调控Wnt/β-catenin信号通路的分子机制及其在肝细胞癌中功能的研究

项目编号： No.81502080

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 张贺云

作者单位： 中山大学

项目金额： 17万元

中文摘要： 组蛋白甲基转移酶SMYD3能特异性地催化组蛋白H3第4位赖氨酸甲基化，促进肿瘤细胞的增殖、侵袭与转移。我们前期研究发现：①肝癌组织中SMYD3的表达水平显著高于癌旁组织，而高表达SMYD3的肝癌患者肿瘤微血管浸润发生率较高，无瘤生存率及总体生存率较低；②过表达SMYD3基因的肝癌细胞具有更强的增殖、克隆形成和迁移能力。③在肝癌细胞中，β-catenin的蛋白水平随着SMYD3的过表达而升高。由此我们提出全新假说：SMYD3通过表观遗传学调控，提高了β-catenin的水平，激活Wnt/β-catenin信号通路，从而促进肝癌的发生发展。.本课题将从β-catenin的转录调控及蛋白稳定性调控等方面来进一步研究SMYD3调控β-catenin的分子机制及其在肝细胞癌中的作用。通过以上研究，将从表观遗传学的角度阐明SMYD3在肝癌发生发展中的作用及其具体分子机制。

中文关键词： 肝细胞癌；组蛋白甲基转移酶；SMYD3；β-catenin

英文摘要： SET and MYND domain-containing protein 3 (SMYD3) was a histone H3-lysine 4-specific methyltransferase， playing an important role in promoting the proliferation, invasion and metastasis of malignant cell. In the previous studies, we found that: ① SMYD3 was upregulated in the most of HCC samples. High expression of SMYD3 was closely correlated with microvascular invasion,lower disease-free survival and overall survival in HCC patients; ② Hepatoma cell lines that overexpressed SMYD3 gene had stronger ability of proliferation, colony formation and migration. ③ The protein levels of β-catenin and were increased with the enhanced expression of SMYD3 in the Hepatoma cell lines. So, we propose a new hypothesis that SMYD3 might through epigenetic regulation to improve the level of β-catenin, which contributed to the development of hepatocellular carcinoma eventually.. In this project, we will study inside the role of SMYD3 in the development of HCC and the regulation mechanism of SMYD3 for β-catenin. Through these studies, we will clarify the role and molecular mechanism of SMYD3 in HCC, which will be helpful for understanding the epigenetic regulatory mechanisms of HCC.

英文关键词： Hepatocellular carcinoma;histone methyltransferases;SMYD3;β-catenin