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G6PD在HBV相關(guān)性肝癌發(fā)生中的作用研究

發(fā)布時(shí)間:2018-03-26 16:49

  本文選題:乙型肝炎病毒 切入點(diǎn):肝細(xì)胞癌 出處:《重慶醫(yī)科大學(xué)》2014年碩士論文


【摘要】:肝細(xì)胞癌(HCC)是全球?qū)嶓w器官惡性腫瘤導(dǎo)致死亡的主要原因之一,慢性乙型肝炎病毒(HBV)感染是其主要危險(xiǎn)因素之一。我們使用iTRAQ聯(lián)合質(zhì)譜技術(shù),為了鑒定新的參與肝癌致病的蛋白這一治療靶標(biāo),在肝臟腫瘤組織與相鄰的非瘤組織中去識(shí)別差異表達(dá)的蛋白。我們對(duì)9個(gè)乙肝病毒相關(guān)性肝癌患者的樣本進(jìn)行了分析?偣1607個(gè)蛋白質(zhì)被鑒定,其中發(fā)現(xiàn)222蛋白質(zhì)在腫瘤樣品中差異性表達(dá)。并且,,我們還驗(yàn)證了其中幾個(gè)蛋白的表達(dá)差異,采用的驗(yàn)證方法為實(shí)時(shí)熒光定量PCR、蛋白質(zhì)印跡法(Western Blot)以及免疫組化技術(shù)。然后,我們選取了一個(gè)在肝癌樣品中的高表達(dá)的蛋白質(zhì):葡萄糖-6-磷酸脫氫酶(G6PD),通過siRNA基因沉默對(duì)其進(jìn)行功能分析。我們發(fā)現(xiàn),G6PD基因沉默通過干擾素信號(hào)通路導(dǎo)致HBV的復(fù)制降低近乎5倍;并且,G6PD基因沉默還抑制了肝癌細(xì)胞在體外遷移和侵襲?傊覀兊难芯拷Y(jié)果提供肝癌發(fā)展機(jī)制的信息,并預(yù)示著抑制葡萄糖-6-磷酸脫氫酶的表達(dá)可能在開發(fā)新的癌癥治療藥物中是一個(gè)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.
【學(xué)位授予單位】:重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2014
【分類號(hào)】:R512.6;R735.7

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 Isabel Fabregat;;Dysregulation of apoptosis in hepatocellular carcinoma cells[J];World Journal of Gastroenterology;2009年05期



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