G6PD在HBV相关性肝癌发生中的作用研究

发布时间：2018-03-26 16:49

本文选题：乙型肝炎病毒　切入点：肝细胞癌　出处：《重庆医科大学》2014年硕士论文

【摘要】：肝细胞癌（HCC）是全球实体器官恶性肿瘤导致死亡的主要原因之一，慢性乙型肝炎病毒（HBV）感染是其主要危险因素之一。我们使用iTRAQ联合质谱技术，为了鉴定新的参与肝癌致病的蛋白这一治疗靶标，在肝脏肿瘤组织与相邻的非瘤组织中去识别差异表达的蛋白。我们对9个乙肝病毒相关性肝癌患者的样本进行了分析。总共1607个蛋白质被鉴定，其中发现222蛋白质在肿瘤样品中差异性表达。并且，，我们还验证了其中几个蛋白的表达差异，采用的验证方法为实时荧光定量PCR、蛋白质印迹法（Western Blot）以及免疫组化技术。然后，我们选取了一个在肝癌样品中的高表达的蛋白质：葡萄糖-6-磷酸脱氢酶（G6PD），通过siRNA基因沉默对其进行功能分析。我们发现，G6PD基因沉默通过干扰素信号通路导致HBV的复制降低近乎5倍；并且，G6PD基因沉默还抑制了肝癌细胞在体外迁移和侵袭。总之，我们的研究结果提供肝癌发展机制的信息，并预示着抑制葡萄糖-6-磷酸脱氢酶的表达可能在开发新的癌症治疗药物中是一个有希望的的策略。
[Abstract]:Hepatocellular carcinoma (HCC) is one of the leading causes of death caused by solid organ malignancies worldwide, and chronic hepatitis B virus (HBV) infection is one of the major risk factors. In order to identify a new protein involved in the pathogenesis of liver cancer as a therapeutic target, To identify differentially expressed proteins in liver tumor tissues and adjacent non-tumor tissues. We analyzed 9 samples from patients with hepatitis B virus associated liver cancer. A total of 1607 proteins were identified. It was found that 222 protein was differentially expressed in tumor samples, and we also verified the differences in the expression of several of the proteins, using real-time fluorescent quantitative PCR, Western blot Western blot and immunohistochemical technique. We selected a highly expressed protein in liver cancer samples: glucose-6-phosphate dehydrogenase (G6PDN) and analyzed its function by siRNA gene silencing. We found that G6PD gene silencing induced HBV by interferon signaling pathway. The replication was reduced by nearly 5 times. Furthermore, the silencing of G6PD gene inhibits the migration and invasion of hepatoma cells in vitro. In conclusion, our findings provide information on the mechanism of liver cancer development. It suggests that inhibiting the expression of glucose-6-phosphate dehydrogenase may be a promising strategy in the development of new cancer treatment drugs.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R512.6;R735.7

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