鼻咽癌转移的线粒体蛋白质组研究
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摘要
目的：分析和鉴定鼻咽癌转移中线粒体蛋白质组的改变,筛选与鼻咽癌转移相关的线粒体蛋白质,为进一步揭示它们参与鼻咽癌转移的分子机制和找寻与鼻咽癌转移相关的特异性分子标志物提供基础。
方法：分别从鼻咽癌5-8F和6-10B细胞中分离线粒体,鉴定其纯度,提取线粒体蛋白质。经2D-DIGE技术找出两种细胞的线粒体差异蛋白质,进行MALDI-TOF和ESI-Q-TOF质谱分析,查询数据库鉴定。同时采用生物信息学方法对线粒体差异蛋白质进行GO功能富集分析和蛋白质相互作用网络构建。并对鼻咽癌5-8F细胞中表达上调的部分线粒体差异蛋白质进行siRNA瞬时干扰,Transwell迁移实验观察细胞运动能力的变化。
结果：包括PRDX3和SOD2在内的16种线粒体差异蛋白质得到鉴定。在鼻咽癌5-8F细胞中抑制PRDX3的表达能够提高细胞的运动能力。GO功能富集分析显示生物学过程主要表现在细胞对活性氧应答反应、过氧化氢代谢过程、线粒体膜电势调控、细胞氧化还原动态平衡和氧化还原作用等5个方面；分子功能主要表现在氧化还原酶活性、半胱氨酸蛋白酶抑制剂活性、过氧化物酶活性、质膜通道蛋白活性和抗氧化剂活性等5个方面。经过数据挖掘,构建了一个线粒体差异蛋白质相互作用的网络。结合肿瘤-间质共演变假说的观点进行分析,初步揭示了PRDX3、PRDX6、SOD2、ECH1、SERPINB5、COX5A、 PDIA5、EIF5A、IDH3B和PSMC4等10种线粒体差异蛋白质参与鼻咽癌转移的可能分子机制,为氧化应激直接促进肿瘤转移的观点提供了实验证据。
结论：共鉴定了16种线粒体差异表达蛋白质,初步揭示了其中10种参与肿瘤转移的可能分子机制。在鼻咽癌5-8F细胞中抑制PRDX3的表达能够提高细胞的运动能力。它们有可能成为鼻咽癌转移的分子标志,在线粒体氧化应激诱导的鼻咽癌转移过程中发挥重要作用。
Background:Mitochondrial proteomic alterations of nasopharyngeal carcinoma metastasis remain unknown. Our purpose is to screen mitochondrial proteins for the elucidation of the molecular mechanisms of nasopharyngeal carcinoma metastasis and the discovery of metastasis-related biomarkers.
Methods:Mitochondria were isolated from nasopharyngeal carcinoma metastatic (5-8F) and nonmetastatic (6-1OB) cell lines, respectively. After characterization of isolated mitochondria, mitochondrial differentially expressed proteins (DEPs) were quantified by two-dimensional difference in-gel electrophoresis (2D-DIGE), and identified by peptide mass fingerprint (PMF) and tandem mass spectrometry (MS/MS). A functional enrichment analysis and a protein-protein interaction network analysis for DEPs were carried out with bioinformatics. Furthermore, siRNAs transient transfections were used to suppress expressions of some up-regulated DEPs in metastatic cells (5-8F), followed by Transwell Migration assay.
Results:Sixteen mitochondrial DEPs including PRDX3and SOD2were identified. Those5-8F cells with suppression of PRDX3showed an increased mobility potential. The functional enrichment analyses of DEPs discovered five significant biological processes including cellular response to reactive oxygen species, hydrogen peroxide metabolic process, regulation of mitochondrial membrane potential, cell redox homeostasis and oxidation reduction, and five significant molecular functions including oxidoreductase activity, caspase inhibitor activity, peroxiredoxin activity, porin activity and antioxidant activity. A protein-protein interaction network of DEPs was generated with literature data. Ten mitochondrial DEPs including PRDX3, PRDX6, SOD2, ECH1, SERPINB5, COX5A, PDIA5, EIF5A, IDH3B, and PSMC4were rationalized in the tumor-stroma co-evolution model that mitochondrial oxidative stress directly contributes to tumor metastasis.
Conclusions:Sixteen mitochondrial DEPs were identified with mass spectrometry and ten of them were rationalized in the tumor-stroma co-evolution model. Those5-8F cells with suppression of PRDX3showed an increased mobility potential. These data suggest that those mitochondrial DEPs are potential biomarkers for NPC metastasis, and their dysregulation would play important roles in mitochondria oxidative stress-mediated NPC metastatic process.
方法：分别从鼻咽癌5-8F和6-10B细胞中分离线粒体,鉴定其纯度,提取线粒体蛋白质。经2D-DIGE技术找出两种细胞的线粒体差异蛋白质,进行MALDI-TOF和ESI-Q-TOF质谱分析,查询数据库鉴定。同时采用生物信息学方法对线粒体差异蛋白质进行GO功能富集分析和蛋白质相互作用网络构建。并对鼻咽癌5-8F细胞中表达上调的部分线粒体差异蛋白质进行siRNA瞬时干扰,Transwell迁移实验观察细胞运动能力的变化。
结果：包括PRDX3和SOD2在内的16种线粒体差异蛋白质得到鉴定。在鼻咽癌5-8F细胞中抑制PRDX3的表达能够提高细胞的运动能力。GO功能富集分析显示生物学过程主要表现在细胞对活性氧应答反应、过氧化氢代谢过程、线粒体膜电势调控、细胞氧化还原动态平衡和氧化还原作用等5个方面；分子功能主要表现在氧化还原酶活性、半胱氨酸蛋白酶抑制剂活性、过氧化物酶活性、质膜通道蛋白活性和抗氧化剂活性等5个方面。经过数据挖掘,构建了一个线粒体差异蛋白质相互作用的网络。结合肿瘤-间质共演变假说的观点进行分析,初步揭示了PRDX3、PRDX6、SOD2、ECH1、SERPINB5、COX5A、 PDIA5、EIF5A、IDH3B和PSMC4等10种线粒体差异蛋白质参与鼻咽癌转移的可能分子机制,为氧化应激直接促进肿瘤转移的观点提供了实验证据。
结论：共鉴定了16种线粒体差异表达蛋白质,初步揭示了其中10种参与肿瘤转移的可能分子机制。在鼻咽癌5-8F细胞中抑制PRDX3的表达能够提高细胞的运动能力。它们有可能成为鼻咽癌转移的分子标志,在线粒体氧化应激诱导的鼻咽癌转移过程中发挥重要作用。
Background:Mitochondrial proteomic alterations of nasopharyngeal carcinoma metastasis remain unknown. Our purpose is to screen mitochondrial proteins for the elucidation of the molecular mechanisms of nasopharyngeal carcinoma metastasis and the discovery of metastasis-related biomarkers.
Methods:Mitochondria were isolated from nasopharyngeal carcinoma metastatic (5-8F) and nonmetastatic (6-1OB) cell lines, respectively. After characterization of isolated mitochondria, mitochondrial differentially expressed proteins (DEPs) were quantified by two-dimensional difference in-gel electrophoresis (2D-DIGE), and identified by peptide mass fingerprint (PMF) and tandem mass spectrometry (MS/MS). A functional enrichment analysis and a protein-protein interaction network analysis for DEPs were carried out with bioinformatics. Furthermore, siRNAs transient transfections were used to suppress expressions of some up-regulated DEPs in metastatic cells (5-8F), followed by Transwell Migration assay.
Results:Sixteen mitochondrial DEPs including PRDX3and SOD2were identified. Those5-8F cells with suppression of PRDX3showed an increased mobility potential. The functional enrichment analyses of DEPs discovered five significant biological processes including cellular response to reactive oxygen species, hydrogen peroxide metabolic process, regulation of mitochondrial membrane potential, cell redox homeostasis and oxidation reduction, and five significant molecular functions including oxidoreductase activity, caspase inhibitor activity, peroxiredoxin activity, porin activity and antioxidant activity. A protein-protein interaction network of DEPs was generated with literature data. Ten mitochondrial DEPs including PRDX3, PRDX6, SOD2, ECH1, SERPINB5, COX5A, PDIA5, EIF5A, IDH3B, and PSMC4were rationalized in the tumor-stroma co-evolution model that mitochondrial oxidative stress directly contributes to tumor metastasis.
Conclusions:Sixteen mitochondrial DEPs were identified with mass spectrometry and ten of them were rationalized in the tumor-stroma co-evolution model. Those5-8F cells with suppression of PRDX3showed an increased mobility potential. These data suggest that those mitochondrial DEPs are potential biomarkers for NPC metastasis, and their dysregulation would play important roles in mitochondria oxidative stress-mediated NPC metastatic process.
引文
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[2]宋立兵,汪慧民,曾木圣,李满枝,简少文：鼻咽癌细胞株SUNE-1异质性研究。癌症1998,17(5)：324-327。
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