FASN在乙型肝炎病毒相关性肝癌迁移侵袭过程中的作用机制研究

发布时间：2018-03-25 06:24

本文选题：肝癌　切入点：FASN　出处：《重庆医科大学》2017年硕士论文

【摘要】：肝癌是全世界癌症死亡的最主要原因之一。由于其高度的转移倾向,活跃的血管生成和快速增殖,复发和较差的预后成为了肝癌治疗及治愈的主要障碍。为了进一步研究FASN肿瘤细胞迁移、侵袭的机制,我们在本研究中,利用免疫组织化学、组织芯片、Transwell和划痕实验等实验技术验证了以前的研究结果,在肝癌组织样品中FASN的表达明显高于非癌组织样品(癌旁),并影响肝癌细胞迁移、侵袭能力。收集敲除及未敲除FASN乙肝相关性肝癌细胞(HepG2.2.15)的分泌蛋白后,使用同位素标记相对和绝对定量(iTRAQ)技术以及质谱分析的方法分析鉴定差异表达的蛋白(DEPS)。我们一共识别出了30种有意义的DEP,其中8种蛋白明显上调,22种蛋白明显下调。经过RT-PCR和Western blotting分析验证,DEP的结果与iTRAQ一致。抑制FASN可以明显降低IGFBP1水平,同时我们发现HIF-1α的表达,活性以及泛素化作用也明显下降。因此,抑制FASN可通过降低IGFBP1表达和HIF-1α的表达、活性及泛素化作用,抑制肝癌细胞迁移,侵袭和愈合。
[Abstract]:Liver cancer is one of the leading causes of cancer death in the world. Recurrence and poor prognosis have become major obstacles to the treatment and cure of liver cancer. In order to further study the mechanism of migration and invasion of FASN tumor cells, we used immunohistochemistry in this study. Tissue microarray Transwell and scratch test were used to verify the results of previous studies. The expression of FASN in HCC tissues was significantly higher than that in non-cancerous tissues (paracarcinoma) and affected the migration of HCC cells. Invasive ability. The secreted proteins of FASN HepG2.2.15 cells were collected after knockout and non-knockout. Relative and absolute quantitative iTRAQ techniques and mass spectrometry were used to analyze and identify the differentially expressed proteins. We identified a total of 30 significant DEPs, of which 8 proteins significantly up-regulated 22 proteins. The results of RT-PCR and Western blotting analysis were consistent with that of iTRAQ. Inhibition of FASN could significantly reduce IGFBP1 level. At the same time, we found that the expression, activity and ubiquification of HIF-1 伪 also decreased significantly. Therefore, inhibition of FASN can inhibit the migration, invasion and healing of hepatoma cells by reducing the expression of IGFBP1 and the expression, activity and ubiquification of HIF-1 伪.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R512.62;R735.7

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