Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Jinan University, Shenzhen, Guangdong 518020, PR China; Institute of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, China.
Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Jinan University, Shenzhen, Guangdong 518020, PR China.
J Proteomics. 2022 Jun 30;262:104598. doi: 10.1016/j.jprot.2022.104598. Epub 2022 Apr 27.
Lysine acetylation (Kac) on histone promotes relaxation of the chromatin conformation and favors gene transcription to regulate oncogenesis, whereas the total acetylation profiling of oral squamous cell carcinoma (OSCC) is unknown. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was utilised to investigate lysine acetylation features of tumor tissues and adjacent normal tissues from 9 patients with OCSS. 282 upregulated Kac sites in 234 proteins and 235 downregulated Kac sites in 162 proteins between OSCC tissues and paired adjacent normal tissues were identified. Different acetylation proteins (DAPs) were analyzed through KEGG-based and MCODE. These DAPs are enriched in the ribosome biogenesis pathway. Survival Analysis of hub genes with TCGA database was performed. In addition, IPA software was used to explore the connection between 9 core DAPs (RPS3, RPL24, RPL19, EIF4A2, RPL12, MYBPC1, RPS6, ARCN1, and TMEM9) and the different expression of KATs and KDACs identified in our proteomic. The study is the first comparative study of Kac modification on oral squamous cell carcinoma. We propose to put forward the hypothesis that the dysfunction of ribosome biogenesis caused by the change of Lysine acetylation, especially downregulated acetylation on RPS6 and RPS3 may associated with the pathogenesis of OSCC. SIGNIFICANCE: The study is the first comparative study of Kac modification on oral squamous cell carcinoma through LC-MS/MS-based modified proteomic. These DAPs are high enriched in the ribosome biogenesis pathway. Used MCODE and survival analysis, 9 core DAPs (RPS3, RPL24, RPL19, EIF4A2, RPL12, MYBPC1, RPS6, ARCN1, and TMEM9) were screened. IPA software was used to explore the connection between 9 core DAPs and the different expression of KATs and KDACs identified in our proteomic. In addition, we propose to put forward the hypothesis that the dysfunction of ribosome biogenesis caused by the change of Lysine acetylation, especially downregulated acetylation on RPS6 and RPS3 may associated with the pathogenesis of OSCC.
赖氨酸乙酰化（Kac）在组蛋白上促进染色质构象的松弛，并有利于基因转录以调节肿瘤发生，而口腔鳞状细胞癌（OSCC）的总乙酰化谱尚不清楚。利用液相色谱-串联质谱（LC-MS/MS）技术，对 9 例 OSCC 患者肿瘤组织和相邻正常组织的赖氨酸乙酰化特征进行了研究。在 OSCC 组织和配对的相邻正常组织之间，鉴定出 282 个上调的 Kac 位点（在 234 种蛋白质中）和 235 个下调的 Kac 位点（在 162 种蛋白质中）。通过基于 KEGG 和 MCODE 的分析，发现了不同的乙酰化蛋白（DAPs）。这些 DAPs 在核糖体生物发生途径中富集。利用 TCGA 数据库对核心基因进行生存分析。此外，还使用 IPA 软件探讨了 9 个核心 DAP（RPS3、RPL24、RPL19、EIF4A2、RPL12、MYBPC1、RPS6、ARCN1 和 TMEM9）与我们蛋白质组学中鉴定的 KAT 和 KDAC 不同表达之间的联系。本研究是口腔鳞状细胞癌中赖氨酸乙酰化修饰的首次比较研究。我们提出假设，赖氨酸乙酰化改变引起的核糖体生物发生功能障碍，特别是 RPS6 和 RPS3 下调的乙酰化可能与 OSCC 的发病机制有关。
本研究是通过基于 LC-MS/MS 的改良蛋白质组学对口腔鳞状细胞癌中 Kac 修饰的首次比较研究。这些 DAP 在核糖体生物发生途径中高度富集。使用 MCODE 和生存分析筛选出 9 个核心 DAP（RPS3、RPL24、RPL19、EIF4A2、RPL12、MYBPC1、RPS6、ARCN1 和 TMEM9）。IPA 软件用于探讨 9 个核心 DAP 与我们蛋白质组学中鉴定的 KAT 和 KDAC 不同表达之间的联系。此外，我们提出假设，赖氨酸乙酰化改变引起的核糖体生物发生功能障碍，特别是 RPS6 和 RPS3 下调的乙酰化可能与 OSCC 的发病机制有关。
