本文選題：鼻咽癌 + 腫瘤轉(zhuǎn)移　； 參考：《中南大學(xué)》2013年博士論文

【摘要】：目的：分析和鑒定鼻咽癌轉(zhuǎn)移中線粒體蛋白質(zhì)組的改變,篩選與鼻咽癌轉(zhuǎn)移相關(guān)的線粒體蛋白質(zhì),為進(jìn)一步揭示它們參與鼻咽癌轉(zhuǎn)移的分子機(jī)制和找尋與鼻咽癌轉(zhuǎn)移相關(guān)的特異性分子標(biāo)志物提供基礎(chǔ)。 方法：分別從鼻咽癌5-8F和6-10B細(xì)胞中分離線粒體,鑒定其純度,提取線粒體蛋白質(zhì)。經(jīng)2D-DIGE技術(shù)找出兩種細(xì)胞的線粒體差異蛋白質(zhì),進(jìn)行MALDI-TOF和ESI-Q-TOF質(zhì)譜分析,查詢數(shù)據(jù)庫鑒定。同時(shí)采用生物信息學(xué)方法對(duì)線粒體差異蛋白質(zhì)進(jìn)行GO功能富集分析和蛋白質(zhì)相互作用網(wǎng)絡(luò)構(gòu)建。并對(duì)鼻咽癌5-8F細(xì)胞中表達(dá)上調(diào)的部分線粒體差異蛋白質(zhì)進(jìn)行siRNA瞬時(shí)干擾,Transwell遷移實(shí)驗(yàn)觀察細(xì)胞運(yùn)動(dòng)能力的變化。 結(jié)果：包括PRDX3和SOD2在內(nèi)的16種線粒體差異蛋白質(zhì)得到鑒定。在鼻咽癌5-8F細(xì)胞中抑制PRDX3的表達(dá)能夠提高細(xì)胞的運(yùn)動(dòng)能力。GO功能富集分析顯示生物學(xué)過程主要表現(xiàn)在細(xì)胞對(duì)活性氧應(yīng)答反應(yīng)、過氧化氫代謝過程、線粒體膜電勢(shì)調(diào)控、細(xì)胞氧化還原動(dòng)態(tài)平衡和氧化還原作用等5個(gè)方面；分子功能主要表現(xiàn)在氧化還原酶活性、半胱氨酸蛋白酶抑制劑活性、過氧化物酶活性、質(zhì)膜通道蛋白活性和抗氧化劑活性等5個(gè)方面。經(jīng)過數(shù)據(jù)挖掘,構(gòu)建了一個(gè)線粒體差異蛋白質(zhì)相互作用的網(wǎng)絡(luò)。結(jié)合腫瘤-間質(zhì)共演變假說的觀點(diǎn)進(jìn)行分析,初步揭示了PRDX3、PRDX6、SOD2、ECH1、SERPINB5、COX5A、 PDIA5、EIF5A、IDH3B和PSMC4等10種線粒體差異蛋白質(zhì)參與鼻咽癌轉(zhuǎn)移的可能分子機(jī)制,為氧化應(yīng)激直接促進(jìn)腫瘤轉(zhuǎn)移的觀點(diǎn)提供了實(shí)驗(yàn)證據(jù)。 結(jié)論：共鑒定了16種線粒體差異表達(dá)蛋白質(zhì),初步揭示了其中10種參與腫瘤轉(zhuǎn)移的可能分子機(jī)制。在鼻咽癌5-8F細(xì)胞中抑制PRDX3的表達(dá)能夠提高細(xì)胞的運(yùn)動(dòng)能力。它們有可能成為鼻咽癌轉(zhuǎn)移的分子標(biāo)志,在線粒體氧化應(yīng)激誘導(dǎo)的鼻咽癌轉(zhuǎn)移過程中發(fā)揮重要作用。
[Abstract]:Objective: to analyze and identify the changes of mitochondrial proteome in metastasis of nasopharyngeal carcinoma (NPC), and to screen the mitochondrial proteins associated with metastasis of nasopharyngeal carcinoma (NPC). It provides a basis for further revealing the molecular mechanism of their involvement in the metastasis of nasopharyngeal carcinoma and finding specific molecular markers related to metastasis of nasopharyngeal carcinoma. Methods: mitochondria were isolated from 5-8F and 6-10B cells of nasopharyngeal carcinoma, their purity was identified and mitochondrial protein was extracted. Mitochondrial differential proteins were identified by 2D-DIGE technique and analyzed by MALDI-TOF and ESI-Q-TOF mass spectrometry. At the same time, bioinformatics was used to analyze mitochondrial differential proteins by go function enrichment analysis and protein interaction network construction. The expression of some mitochondrial differentially expressed proteins in 5-8F cells of nasopharyngeal carcinoma (NPC) was assayed by siRNA transient interference transwell migration assay. Results: sixteen mitochondrial differential proteins including PRDX3 and SOD2 were identified. Inhibition of PRDX3 expression in 5-8F cells of nasopharyngeal carcinoma (NPC) showed that inhibition of PRDX3 expression in 5-8F cells could enhance cell motility. Go functional enrichment analysis showed that the biological processes were cell response to reactive oxygen species (Ros), hydrogen peroxide metabolism, and regulation of mitochondrial membrane potential. Cell redox dynamic balance and redox activity, the molecular function mainly manifested in redox enzyme activity, cysteine protease inhibitor activity, peroxidase activity, The activity of plasma membrane channel protein and antioxidant were 5 aspects. Through data mining, a network of mitochondrial differential protein interactions was constructed. Based on the hypothesis of tumor-stromal coevolution, the possible molecular mechanisms of 10 mitochondrial differential proteins, such as PRDX3, PRDX6, SOD2, ECH1, SERPINB5, COX5A, PDIA5EIF5AtIIDH3B and PSMC4, in the metastasis of nasopharyngeal carcinoma were preliminarily revealed. It provides experimental evidence for the view that oxidative stress directly promotes tumor metastasis. Conclusion: a total of 16 mitochondrial differentially expressed proteins were identified, and 10 of them were identified as possible molecular mechanisms involved in tumor metastasis. Inhibition of PRDX3 expression in 5-8 F cells of nasopharyngeal carcinoma can improve cell motility. They may be molecular markers of NPC metastasis and play an important role in mitochondrial oxidative stress-induced metastasis of NPC.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2013
【分類號(hào)】：R739.63

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