食管鳞癌中组蛋白修饰基因突变与基因差异表达的关联和对细胞功能的影响

发布时间：2018-03-27 21:10

本文选题：食管鳞癌　切入点：表观遗传学　出处：《北京协和医学院》2016年博士论文

【摘要】：目的：发现食管鳞癌中组蛋白修饰基因突变组和野生型组之间差异表达的基因,探究其可能的功能；研究组蛋白修饰基因突变对食管鳞癌细胞功能的影响。方法：获取癌症基因组图谱(TCGA)计划公布的食管鳞癌体细胞突变和基因表达数据,综合使用4款生物信息学软件辨识组蛋白修饰基因突变组和野生型组间差异表达的基因,并分析其功能；使用本实验室前期构建的KYSE-150 EP300 KO细胞系,以EP300为代表,研究组蛋白修饰基因突变对食管鳞癌细胞增殖、迁移、侵袭功能的影响。结果：综合4款生物信息学软件,共发现了两组间差异表达的129个基因,主要富集与细胞膜,参与信号传导、细胞对刺激反应等生物过程,涉及p53、Wnt等信号通路；EP300敲除显著降低了KYSE-150细胞系的迁移和侵袭能力。讨论：本实验使用生物信息学的方法辨识了与组蛋白修饰基因突变相关的差异表达基因,食管鳞癌中组蛋白修饰基因的突变可能与抑癌基因的下调、处理氧化还原压力的能力上调、血管新生调节失衡有关,并可能通过以上途径促进食管鳞癌的发生发展。
[Abstract]:Objective: to find the differentially expressed genes between histone modified gene mutation group and wild type group in esophageal squamous cell carcinoma and to explore its possible function. Effects of protein-modified gene mutations on the function of esophageal squamous cell carcinoma cells. Methods: somatic mutation and gene expression data of esophageal squamous cell carcinoma were obtained from the cancer genome map (TCGA) project. Four bioinformatics softwares were used to identify differentially expressed genes between mutant group and wild type group of histone modified gene, and to analyze their functions. EP300 was used as the representative of KYSE-150 EP300 KO cell line constructed in our laboratory. The effect of protein-modified gene mutation on the proliferation, migration and invasion of esophageal squamous cell carcinoma cells was studied. Results: 129 differentially expressed genes were found in four bioinformatics software groups, which were mainly rich in cell membrane. Involved in signal transduction, cell response to stimuli and other biological processes, P53 / Wnt signaling pathway EP300 knockout significantly reduced the migration and invasion of KYSE-150 cell lines. We used bioinformatics to identify differentially expressed genes associated with histone modified gene mutations. The mutation of histone modified gene in esophageal squamous cell carcinoma may be related to the down-regulation of tumor suppressor gene, the up-regulation of redox pressure and the imbalance of angiogenesis, and may promote the occurrence and development of esophageal squamous cell carcinoma through these pathways.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R735.1

【相似文献】