SNRPN异常甲基化在肠癌肝转移中的调控机制

项目名称： SNRPN异常甲基化在肠癌肝转移中的调控机制

项目编号： No.81472228

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： 许剑民

作者单位： 复旦大学

项目金额： 78万元

中文摘要： 大肠癌术后复发转移中肝转移是最常见的转移模式，其内在机制尚未完全阐明。申请者在前期工作中积累了肠癌肝转移个体化治疗的经验，并建立了大肠癌肝转移的特征分子预测模型，在肝转移相关蛋白标志筛查中，发现小核糖核蛋白SNRPN可能是潜在的分子靶标，与肝转移的发生和预后密切相关。我们在前期工作中证实SNRPN在肠癌中存在异常去甲基化，导致基因过度表达，而上调SNRPN能够介导大肠癌肝转移的发生，促进细胞获得运动能力。进一步实验表明：SNRPN下游可调节糖基转移酶，可能存在激活肠癌细胞膜表面半乳糖残基，从而通过与肝细胞膜上特异性受体相互作用而使肠癌细胞定居于肝脏的机制。本项目拟在此基础上，从大规模组织样本中总结SNRPN甲基化模式对于大肠癌肝转移的临床意义和预后价值。同时，在细胞和动物模型中进一步深入探讨其在大肠癌肝转移调控中的作用方式和调控分子机制：解析SNRPN调节半乳糖苷转移酶表达的方式和作用

中文关键词： C08_结；直肠肿瘤；肝转移；SNRPN

英文摘要： Liver metastasis is the most common kind of relapse in colorectal caner ,whereas the mechanism within remains unclearly explained.In our preliminary work,we gathered abundant experience of individualized treatment to CLM and established prediction model with specific molecules in CLM.By screening amounts of proteins related to CLM(colorectal liver metastasis),we found a small nuclear ribonucleoprotein,namely SNRPN,which is clossly related to the occurance and prognosis of CLM, making a potential moleculor target. The aberrant methylation of SNRPN,which has been tested in colorectal cancer,results in the over-expression of SNRPN, which can promote liver metasasisis by the way of gaining cancer cells the ability of movement.Moreover, downstream molecules of SNRPN will moderate glycosyl transferase,and,Then,the changed glycosyl transferase activates galactose residues on colorectal cancer cells,which is likely to settle dowm the coloretal cancer cells in liver by interacting with specific recepters on liver cells.On the above basis,we aim to find the clinical and prognostic significance of methylated SNRPN in CLM through the retorspective analysis of numerous cases from our follow-up database,and futher study will focus on exploring molecular mechaniam,comfirming the functioning way and site of SNRPN in expression of glycosyl transferase in cell and animal experiments.

英文关键词： colorectal cancer;liver metastasis;SNRPN