【摘要】：研究背景和目的:結直腸癌是較為常見的惡性腫瘤,其死亡率位于世界第四位;其發(fā)病率,在男性位于第3位,在女性位于第2位。近年來,隨著我國人民生活水平的提高,結直腸癌的發(fā)病率不斷上升,在上海等發(fā)達地區(qū),結直腸癌已位列惡性腫瘤發(fā)病率第2位。腫瘤的肝肺等遠處轉移是結直腸癌病人死亡的主要原因,盡管新的治療手段,和新藥物的不斷出現(xiàn),但晚期結直腸癌的預后未見明顯改善。此外,高昂的醫(yī)療費用,給很多家庭帶來了較重的經濟壓力,引發(fā)了較多的社會矛盾。雖然結直腸癌是可早期發(fā)現(xiàn)早期治療的,但約1/4的患者首次就診時就出現(xiàn)肝肺等遠處轉移。此外結直腸癌的發(fā)病機制目前仍未清晰,進一步深入研究結直腸癌的發(fā)生發(fā)展機制,可以指導臨床針對性的治療,提高預后。因此,研究結直腸癌新預后相關基因,特別是促癌基因在結直腸癌發(fā)生發(fā)展中的作用和機制可以為結直腸癌預后和復發(fā)提供分子標志物,也可為相應的靶向治療策略建立重要的分子靶點。本研究為探索MTERFD1在結直腸中的作用。方法:1.搜索GEO、TCGA和KaPlan Meier-Plotter數據庫的相關數據進行分析;2.構建了MTERFD1過表達質粒,PCDNA-3.1-MTERFD1。利用過表達質粒和siRNA,采用MTT方法檢測轉染后細胞增殖狀況;流式細胞技術檢測細胞凋亡;3.采用Elisa方法觀察IL-6和IL-11的表達情況;4.采用MTT方法和流式細胞技術檢測檢測照射條件下細胞凋亡和增殖;結果:1.MTERFD1的生物信息學分析MTERFD1在正常組織中低表達,在腫瘤組織中高表達。2.MTERFD1在結直腸癌中的作用的相關研究過表達MTERFD1可促進細胞增殖,敲減MTERFD1可抑制增殖,促進細胞凋亡。3.MTERFD1作用靶點的初步研究上調IL-6和IL-11可促進結直腸癌細胞增殖,下調IL-6和IL-11可抑制結直腸癌細胞凋亡,過表達MTERFD1可上調IL-6和IL-11,敲減MTERFD1可下調IL-6和IL-11。4.MTERFD1與放療之間關系的初步研究照射可上調MTERFD1,過表達MTERFD1可抑制照射后的細胞凋亡。結論:1.MTERFD1可能促進結直腸癌的發(fā)生;2.IL-6、IL-11可能為MTERFD1發(fā)揮作用的靶點。3.高表達MTERFD1的結直腸癌可能對放療不敏感。
[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.
【學位授予單位】：第二軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R735.34

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