MTERFD1在结直肠癌作用中的初步研究

发布时间：2018-10-05 14:54

【摘要】：研究背景和目的:结直肠癌是较为常见的恶性肿瘤,其死亡率位于世界第四位;其发病率,在男性位于第3位,在女性位于第2位。近年来,随着我国人民生活水平的提高,结直肠癌的发病率不断上升,在上海等发达地区,结直肠癌已位列恶性肿瘤发病率第2位。肿瘤的肝肺等远处转移是结直肠癌病人死亡的主要原因,尽管新的治疗手段,和新药物的不断出现,但晚期结直肠癌的预后未见明显改善。此外,高昂的医疗费用,给很多家庭带来了较重的经济压力,引发了较多的社会矛盾。虽然结直肠癌是可早期发现早期治疗的,但约1/4的患者首次就诊时就出现肝肺等远处转移。此外结直肠癌的发病机制目前仍未清晰,进一步深入研究结直肠癌的发生发展机制,可以指导临床针对性的治疗,提高预后。因此,研究结直肠癌新预后相关基因,特别是促癌基因在结直肠癌发生发展中的作用和机制可以为结直肠癌预后和复发提供分子标志物,也可为相应的靶向治疗策略建立重要的分子靶点。本研究为探索MTERFD1在结直肠中的作用。方法:1.搜索GEO、TCGA和KaPlan Meier-Plotter数据库的相关数据进行分析;2.构建了MTERFD1过表达质粒,PCDNA-3.1-MTERFD1。利用过表达质粒和siRNA,采用MTT方法检测转染后细胞增殖状况;流式细胞技术检测细胞凋亡;3.采用Elisa方法观察IL-6和IL-11的表达情况;4.采用MTT方法和流式细胞技术检测检测照射条件下细胞凋亡和增殖;结果:1.MTERFD1的生物信息学分析MTERFD1在正常组织中低表达,在肿瘤组织中高表达。2.MTERFD1在结直肠癌中的作用的相关研究过表达MTERFD1可促进细胞增殖,敲减MTERFD1可抑制增殖,促进细胞凋亡。3.MTERFD1作用靶点的初步研究上调IL-6和IL-11可促进结直肠癌细胞增殖,下调IL-6和IL-11可抑制结直肠癌细胞凋亡,过表达MTERFD1可上调IL-6和IL-11,敲减MTERFD1可下调IL-6和IL-11。4.MTERFD1与放疗之间关系的初步研究照射可上调MTERFD1,过表达MTERFD1可抑制照射后的细胞凋亡。结论:1.MTERFD1可能促进结直肠癌的发生;2.IL-6、IL-11可能为MTERFD1发挥作用的靶点。3.高表达MTERFD1的结直肠癌可能对放疗不敏感。
[Abstract]:Background and objective: colorectal cancer is the most common malignant tumor, and its mortality rate is the fourth in the world, and its morbidity is the third in men and the second in women. In recent years, with the improvement of people's living standard in China, the incidence of colorectal cancer has been rising. In Shanghai and other developed regions, colorectal cancer has ranked second in the incidence of malignant tumors. Distant metastasis of tumor such as liver and lung is the main cause of death in patients with colorectal cancer. Despite the emergence of new treatments and new drugs, the prognosis of advanced colorectal cancer has not been significantly improved. In addition, the high cost of medical care has brought heavy economic pressure to many families and caused more social conflicts. Although early detection of colorectal cancer can be early treatment, about a quarter of patients with the first visit to the liver and lung and other distant metastasis. In addition, the pathogenesis of colorectal cancer is still unclear. Further in-depth study of the pathogenesis of colorectal cancer can guide the clinical targeted treatment and improve the prognosis. Therefore, the study of the role and mechanism of new prognostic genes, in particular oncogenes, in the genesis and development of colorectal cancer, may provide molecular markers for the prognosis and recurrence of colorectal cancer, It can also establish important molecular targets for the corresponding targeted therapy strategies. The purpose of this study was to explore the role of MTERFD1 in colorectal cancer. Method 1: 1. Search GEO,TCGA and KaPlan Meier-Plotter database related data for analysis. MTERFD1 overexpression plasmid PCDNA-3.1-MTERFD1 was constructed. Overexpression plasmids and siRNA, were used to detect the proliferation of transfected cells by MTT and flow cytometry to detect apoptosis. The expression of IL-6 and IL-11 was observed by Elisa method. MTT and flow cytometry were used to detect apoptosis and proliferation of cells exposed to irradiation. Results 1. Bioinformatics of MTERFD1 was used to analyze the low expression of MTERFD1 in normal tissues. The role of overexpression of MTERFD1 in Colorectal Cancer; overexpression of MTERFD1 can promote cell proliferation and knockout of MTERFD1 inhibits proliferation. Preliminary study on the Target of promoting apoptosis. MTERFD1 upregulated IL-6 and IL-11 could promote the proliferation of colorectal cancer cells, and down-regulated IL-6 and IL-11 could inhibit the apoptosis of colorectal cancer cells. Overexpression of MTERFD1 upregulated IL-6 and IL-11, knockout MTERFD1 down-regulated the relationship between IL-6 and IL-11.4.MTERFD1 and radiotherapy; overexpression of MTERFD1, MTERFD1 could inhibit apoptosis after irradiation. Conclusion: 1. MTERFD1 may promote the development of colorectal cancer. 2. IL-6 IL-11 may be the target of MTERFD1. Colorectal cancer with high expression of MTERFD1 may be insensitive to radiotherapy.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.34

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