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Large-Scale Identification of Lysine Crotonylation Reveals Its Potential Role in Oral Squamous Cell Carcinoma
Cancer Management and Research ( IF 3.3 ) Pub Date : 2023-10-17 , DOI: 10.2147/cmar.s424422 Xiteng Yin 1, 2 , Hongbo Zhang 1, 2 , Zheng Wei 2, 3 , Yufeng Wang 1, 2 , Shengwei Han 1, 2 , Meng Zhou 4 , Wenguang Xu 1, 2 , Wei Han 1, 2
Cancer Management and Research ( IF 3.3 ) Pub Date : 2023-10-17 , DOI: 10.2147/cmar.s424422 Xiteng Yin 1, 2 , Hongbo Zhang 1, 2 , Zheng Wei 2, 3 , Yufeng Wang 1, 2 , Shengwei Han 1, 2 , Meng Zhou 4 , Wenguang Xu 1, 2 , Wei Han 1, 2
Affiliation
Purpose: Lysine crotonylation, an emerging posttranslational modification, has been implicated in the regulation of diverse biological processes. However, its involvement in oral squamous cell carcinoma (OSCC) remains elusive. This study aims to reveal the global crotonylome in OSCC under hypoxic conditions and explore the potential regulatory mechanism of crotonylation in OSCC.
Methods: Liquid-chromatography fractionation, affinity enrichment of crotonylated peptides, and high-resolution mass spectrometry were employed to detect differential crotonylation in CAL27 cells cultured under hypoxia. The obtained data were further subjected to bioinformatics analysis to uncover the involved biological processes and pathways of the dysregulated crotonylated proteins. A site-mutated plasmid was utilized to investigate the effect of crotonylation on Heat Shock Protein 90 Alpha Family Class B Member 1 (HAP90AB1) function.
Results: A large-scale crotonylome analysis revealed 1563 crotonylated modification sites on 605 proteins in CAL27 cells under hypoxia. Bioinformatics analysis revealed a significant decrease in histone crotonylation levels, while up-regulated crotonylated proteins were mainly concentrated in non-histone proteins. Notably, glycolysis-related proteins exhibited prominent up-regulation among the identified crotonylated proteins, with HSP90AB1 displaying the most significant changes. Subsequent experimental findings confirmed that mutating lysine 265 of HSP90AB1 into a silent arginine impaired its function in promoting glycolysis.
Conclusion: Our study provides insights into the crotonylation modification of proteins in OSCC under hypoxic conditions and elucidates the associated biological processes and pathways. Crotonylation of HSP90AB1 in hypoxic conditions may enhance the glycolysis regulation ability in OSCC, offering novel perspectives on the regulatory mechanism of crotonylation in hypoxic OSCC and potential therapeutic targets for OSCC treatment.
Keywords: crotonylation, hypoxia, oral squamous cell carcinoma, glycolysis, heat shock protein 90 alpha family class B member 1
中文翻译：
赖氨酸巴豆酰化的大规模鉴定揭示了其在口腔鳞状细胞癌中的潜在作用
目的：赖氨酸巴豆酰化是一种新兴的翻译后修饰，与多种生物过程的调节有关。然而，它与口腔鳞状细胞癌（OSCC）的关系仍然难以捉摸。本研究旨在揭示缺氧条件下口腔鳞癌的整体巴豆酰化基因组，探讨口腔鳞癌中巴豆酰化的潜在调控机制。
方法：采用液相色谱分级分离、巴豆酰化肽亲和富集和高分辨率质谱法检测缺氧培养的CAL27细胞中巴豆酰化的差异。获得的数据进一步进行生物信息学分析，以揭示失调的巴豆酰化蛋白所涉及的生物过程和途径。利用位点突变质粒研究巴豆酰化对热休克蛋白 90 Alpha 家族 B 类成员 1 (HAP90AB1) 功能的影响。
结果：大规模巴豆酰化组分析揭示了缺氧条件下 CAL27 细胞中 605 个蛋白质上有 1563 个巴豆酰化修饰位点。生物信息学分析显示组蛋白巴豆酰化水平显着下降，而上调的巴豆酰化蛋白主要集中在非组蛋白蛋白中。值得注意的是，在已鉴定的巴豆酰化蛋白中，糖酵解相关蛋白表现出显着的上调，其中 HSP90AB1 显示出最显着的变化。随后的实验结果证实，将HSP90AB1的第265位赖氨酸突变为沉默的精氨酸会损害其促进糖酵解的功能。
结论：我们的研究提供了对缺氧条件下 OSCC 中蛋白质巴豆酰化修饰的见解，并阐明了相关的生物过程和途径。缺氧条件下 HSP90AB1 的巴豆酰化可能增强 OSCC 的糖酵解调节能力，为缺氧 OSCC 中巴豆酰化的调节机制和 OSCC 治疗的潜在治疗靶点提供新的视角。
关键词：巴豆酰化，缺氧，口腔鳞状细胞癌，糖酵解，热休克蛋白90α家族B类成员1
更新日期：2023-10-17
Methods: Liquid-chromatography fractionation, affinity enrichment of crotonylated peptides, and high-resolution mass spectrometry were employed to detect differential crotonylation in CAL27 cells cultured under hypoxia. The obtained data were further subjected to bioinformatics analysis to uncover the involved biological processes and pathways of the dysregulated crotonylated proteins. A site-mutated plasmid was utilized to investigate the effect of crotonylation on Heat Shock Protein 90 Alpha Family Class B Member 1 (HAP90AB1) function.
Results: A large-scale crotonylome analysis revealed 1563 crotonylated modification sites on 605 proteins in CAL27 cells under hypoxia. Bioinformatics analysis revealed a significant decrease in histone crotonylation levels, while up-regulated crotonylated proteins were mainly concentrated in non-histone proteins. Notably, glycolysis-related proteins exhibited prominent up-regulation among the identified crotonylated proteins, with HSP90AB1 displaying the most significant changes. Subsequent experimental findings confirmed that mutating lysine 265 of HSP90AB1 into a silent arginine impaired its function in promoting glycolysis.
Conclusion: Our study provides insights into the crotonylation modification of proteins in OSCC under hypoxic conditions and elucidates the associated biological processes and pathways. Crotonylation of HSP90AB1 in hypoxic conditions may enhance the glycolysis regulation ability in OSCC, offering novel perspectives on the regulatory mechanism of crotonylation in hypoxic OSCC and potential therapeutic targets for OSCC treatment.
Keywords: crotonylation, hypoxia, oral squamous cell carcinoma, glycolysis, heat shock protein 90 alpha family class B member 1
中文翻译：
赖氨酸巴豆酰化的大规模鉴定揭示了其在口腔鳞状细胞癌中的潜在作用
目的：赖氨酸巴豆酰化是一种新兴的翻译后修饰，与多种生物过程的调节有关。然而，它与口腔鳞状细胞癌（OSCC）的关系仍然难以捉摸。本研究旨在揭示缺氧条件下口腔鳞癌的整体巴豆酰化基因组，探讨口腔鳞癌中巴豆酰化的潜在调控机制。
方法：采用液相色谱分级分离、巴豆酰化肽亲和富集和高分辨率质谱法检测缺氧培养的CAL27细胞中巴豆酰化的差异。获得的数据进一步进行生物信息学分析，以揭示失调的巴豆酰化蛋白所涉及的生物过程和途径。利用位点突变质粒研究巴豆酰化对热休克蛋白 90 Alpha 家族 B 类成员 1 (HAP90AB1) 功能的影响。
结果：大规模巴豆酰化组分析揭示了缺氧条件下 CAL27 细胞中 605 个蛋白质上有 1563 个巴豆酰化修饰位点。生物信息学分析显示组蛋白巴豆酰化水平显着下降，而上调的巴豆酰化蛋白主要集中在非组蛋白蛋白中。值得注意的是，在已鉴定的巴豆酰化蛋白中，糖酵解相关蛋白表现出显着的上调，其中 HSP90AB1 显示出最显着的变化。随后的实验结果证实，将HSP90AB1的第265位赖氨酸突变为沉默的精氨酸会损害其促进糖酵解的功能。
结论：我们的研究提供了对缺氧条件下 OSCC 中蛋白质巴豆酰化修饰的见解，并阐明了相关的生物过程和途径。缺氧条件下 HSP90AB1 的巴豆酰化可能增强 OSCC 的糖酵解调节能力，为缺氧 OSCC 中巴豆酰化的调节机制和 OSCC 治疗的潜在治疗靶点提供新的视角。
关键词：巴豆酰化，缺氧，口腔鳞状细胞癌，糖酵解，热休克蛋白90α家族B类成员1
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