【摘要】：研究背景和目的:結(jié)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(jié)直腸癌的發(fā)病率不斷上升,在上海等發(fā)達(dá)地區(qū),結(jié)直腸癌已位列惡性腫瘤發(fā)病率第2位。腫瘤的肝肺等遠(yuǎn)處轉(zhuǎn)移是結(jié)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(jié)直腸癌的預(yù)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(jīng)濟(jì)壓力,引發(fā)了較多的社會矛盾。雖然結(jié)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(yuǎn)處轉(zhuǎn)移。此外結(jié)直腸癌的發(fā)病機制目前仍未清晰,進(jìn)一步深入研究結(jié)直腸癌的發(fā)生發(fā)展機制,可以指導(dǎo)臨床針對性的治療,提高預(yù)后。因此,研究結(jié)直腸癌新預(yù)后相關(guān)基因,特別是促癌基因在結(jié)直腸癌發(fā)生發(fā)展中的作用和機制可以為結(jié)直腸癌預(yù)后和復(fù)發(fā)提供分子標(biāo)志物,也可為相應(yīng)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(jié)直腸中的作用。方法:1.搜索GEO、TCGA和KaPlan Meier-Plotter數(shù)據(jù)庫的相關(guān)數(shù)據(jù)進(jìn)行分析;2.構(gòu)建了MTERFD1過表達(dá)質(zhì)粒,PCDNA-3.1-MTERFD1。利用過表達(dá)質(zhì)粒和siRNA,采用MTT方法檢測轉(zhuǎn)染后細(xì)胞增殖狀況;流式細(xì)胞技術(shù)檢測細(xì)胞凋亡;3.采用Elisa方法觀察IL-6和IL-11的表達(dá)情況;4.采用MTT方法和流式細(xì)胞技術(shù)檢測檢測照射條件下細(xì)胞凋亡和增殖;結(jié)果:1.MTERFD1的生物信息學(xué)分析MTERFD1在正常組織中低表達(dá),在腫瘤組織中高表達(dá)。2.MTERFD1在結(jié)直腸癌中的作用的相關(guān)研究過表達(dá)MTERFD1可促進(jìn)細(xì)胞增殖,敲減MTERFD1可抑制增殖,促進(jìn)細(xì)胞凋亡。3.MTERFD1作用靶點的初步研究上調(diào)IL-6和IL-11可促進(jìn)結(jié)直腸癌細(xì)胞增殖,下調(diào)IL-6和IL-11可抑制結(jié)直腸癌細(xì)胞凋亡,過表達(dá)MTERFD1可上調(diào)IL-6和IL-11,敲減MTERFD1可下調(diào)IL-6和IL-11。4.MTERFD1與放療之間關(guān)系的初步研究照射可上調(diào)MTERFD1,過表達(dá)MTERFD1可抑制照射后的細(xì)胞凋亡。結(jié)論:1.MTERFD1可能促進(jìn)結(jié)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(dá)MTERFD1的結(jié)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(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R735.34

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