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定量全局蛋白质组学和赖氨酸琥珀酰化组学分析揭示了能量代谢在肾细胞癌中的作用。

Quantitative Global Proteome and Lysine Succinylome Analyses Reveal the Effects of Energy Metabolism in Renal Cell Carcinoma.

机构信息

Department of Urology, The First Hospital of China Medical University, Shenyang, 110001, P. R. China.

Institute of Urology, The First Hospital of China Medical University, Shenyang, 110001, P. R. China.

出版信息

Proteomics. 2018 Oct;18(19):e1800001. doi: 10.1002/pmic.201800001. Epub 2018 Sep 5.

DOI:10.1002/pmic.201800001
PMID:29882248
Abstract

In light of the increasing incidence of renal cell carcinoma (RCC), its molecular mechanisms have been comprehensively explored in numerous recent studies. However, few studies focus on the influence of multi-factor interactions during the occurrence and development of RCC. This study aims to investigate the quantitative global proteome and the changes in lysine succinylation in related proteins, seeking to facilitate a better understanding of the molecular mechanisms underlying RCC. LC-MS/MS combined with bioinformatics analysis are used to quantitatively detect the perspectives at the global protein level. IP and WB analysis were conducted to further verify the alternations of related proteins and lysine succinylation. A total of 3,217 proteins and 1,238 lysine succinylation sites are quantified in RCC tissues, and 668 differentially expressed proteins and 161 differentially expressed lysine succinylation sites are identified. Besides, expressions of PGK1 and PKM2 at protein and lysine, succinylation levels are significantly altered in RCC tissues. Bioinformatics analysis indicates that the glycolysis pathway is a potential mechanism of RCC progression and lysine succinylation may plays a potential role in energy metabolism. These results can provide a new direction for exploring the molecular mechanism of RCC tumorigenesis.

摘要

鉴于肾细胞癌(RCC)发病率的不断上升,最近的许多研究都对其分子机制进行了全面的探讨。然而,很少有研究关注 RCC 发生和发展过程中多种因素相互作用的影响。本研究旨在通过 LC-MS/MS 联合生物信息学分析,对 RCC 相关蛋白的赖氨酸琥珀酰化修饰变化进行定量检测,以期深入了解 RCC 的分子机制。本研究旨在探讨肾细胞癌相关蛋白的定量全蛋白质组学和赖氨酸琥珀酰化修饰变化,以促进对肾细胞癌分子机制的更好理解。本研究采用 LC-MS/MS 联合生物信息学分析方法对 RCC 组织进行了全局蛋白质水平的定量检测。通过 IP 和 WB 分析进一步验证了相关蛋白和赖氨酸琥珀酰化修饰的变化。在 RCC 组织中定量检测到 3217 种蛋白质和 1238 个赖氨酸琥珀酰化位点,鉴定到 668 个差异表达蛋白和 161 个差异表达的赖氨酸琥珀酰化位点。此外,PGK1 和 PKM2 蛋白和赖氨酸琥珀酰化水平在 RCC 组织中表达明显改变。生物信息学分析表明,糖酵解途径可能是 RCC 进展的潜在机制,而赖氨酸琥珀酰化可能在能量代谢中发挥潜在作用。这些结果可为探索 RCC 肿瘤发生的分子机制提供新的方向。

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