癌变过程中C-反应蛋白非编码突变的研究

发布时间：2018-04-20 01:20

本文选题：C-反应蛋白 + -286位点　；参考：《兰州大学》2015年硕士论文

【摘要】：炎症反应和基因组突变可以引发癌症。C-反应蛋白(C-reactive protein, CRP)是一个经典的急性期蛋白,在临床上被广泛用作炎症的非特异性标识物。近年来的研究显示CRP的确和癌症相关,然而对CRP只是伴随癌症发生的炎症指示分子,还是CRP本身参与到癌症的发生发展过程中还存在着争议。对于后者观点的研究有可能成为癌症治疗重要的突破口。我们在实验中偶然发现癌细胞系中CRP非编码区的-286位点的基因型异常,我们推测癌变过程中CRP的该位点发生了突变。为此我们通过对比癌症组织和正常组织,发现了癌症组织中CRP的启动子区的-286SNP位点存在高频率的突变。后续实验又表明此突变通过消除-286位的DNA甲基化,从而上调CRP在肿瘤组织中的表达。而后我们检查发现癌症组织中其他SNP位点并没有类似的突变情况,表明-286SNP位点突变癌变过程中特异性的选择。同时我们检测了结直肠癌中几种常见的基因突变,发现-286SNP突变与p53和k-ras突变不存在相关性,而在直肠癌中-286SNP突变和.APC基因突变显著相关,暗示着肿瘤发生过程中CRP和Wnt信号通路存在相互作用。
[Abstract]:Inflammatory and genomic mutations can cause the cancer.C- reactive protein (C-reactive protein, CRP) as a classic acute phase protein, which is widely used as a nonspecific marker of inflammation. In recent years, studies have shown that CRP is indeed associated with cancer, but CRP is only an inflammatory indicator associated with cancer, or a CRP book. There is still controversy during the development of cancer. Research on the latter may be an important breakthrough in the treatment of cancer. In the experiment, we discovered the genotype of the -286 loci in the CRP non coding region of the cancer cell line, and we speculate that the site of CRP has a mutation during the carcinogenesis. After comparison of cancer tissue and normal tissue, a high frequency mutation was found in the -286SNP site of the promoter region of CRP in cancer tissues. Subsequent experiments showed that the mutation increased the expression of CRP in the tumor tissue by eliminating DNA methylation of the -286 position. The mutation shows the specific selection during the mutation of the -286SNP mutation. We also detected several common gene mutations in colorectal cancer, and found that the -286SNP mutation was not associated with the p53 and K-ras mutations, while the -286SNP mutation and the.APC gene mutation in the rectal cancer were significantly related, suggesting that the tumor occurred during the carcinogenesis of CRP and Wnt. The signal pathways interact with each other.

【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R730.2;Q78

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