Li Penghui, Xue Yuan
Department of Gastrointestinal surgery, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan, China.
Department of thyroid surgery, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan, China.
Front Cell Dev Biol. 2024 Sep 26;12:1447939. doi: 10.3389/fcell.2024.1447939. eCollection 2024.
Recent advances in high-resolution mass spectrometry-based proteomics have improved our understanding of lysine acetylation in proteins, including histones and non-histone proteins. Lysine acetylation, a reversible post-translational modification, is catalyzed by lysine acetyltransferases (KATs) and lysine deacetylases (KDACs). Proteins comprising evolutionarily conserved bromodomains (BRDs) recognize these acetylated lysine residues and consequently activate transcription. Lysine acetylation regulates almost all cellular processes, including transcription, cell cycle progression, and metabolic functions. Studies have reported the aberrant expression, translocation, and mutation of genes encoding lysine acetylation regulators in various cancers, including digestive tract cancers. These dysregulated lysine acetylation regulators contribute to the pathogenesis of digestive system cancers by modulating the expression and activity of cancer-related genes or pathways. Several inhibitors targeting KATs, KDACs, and BRDs are currently in preclinical trials and have demonstrated anti-cancer effects. Digestive tract cancers, including encompass esophageal, gastric, colorectal, liver, and pancreatic cancers, represent a group of heterogeneous malignancies. However, these cancers are typically diagnosed at an advanced stage owing to the lack of early symptoms and are consequently associated with poor 5-year survival rates. Thus, there is an urgent need to identify novel biomarkers for early detection, as well as to accurately predict the clinical outcomes and identify effective therapeutic targets for these malignancies. Although the role of lysine acetylation in digestive tract cancers remains unclear, further analysis could improve our understanding of its role in the pathogenesis of digestive tract cancers. This review aims to summarize the implications and pathogenic mechanisms of lysine acetylation dysregulation in digestive tract cancers, as well as its potential clinical applications.
基于高分辨率质谱的蛋白质组学的最新进展，加深了我们对蛋白质（包括组蛋白和非组蛋白）中赖氨酸乙酰化的理解。赖氨酸乙酰化是一种可逆的翻译后修饰，由赖氨酸乙酰转移酶（KATs）和赖氨酸脱乙酰酶（KDACs）催化。包含进化上保守的溴结构域（BRDs）的蛋白质识别这些乙酰化的赖氨酸残基，从而激活转录。赖氨酸乙酰化调节几乎所有细胞过程，包括转录、细胞周期进程和代谢功能。研究报道了在包括消化道癌症在内的各种癌症中，编码赖氨酸乙酰化调节因子的基因存在异常表达、易位和突变。这些失调的赖氨酸乙酰化调节因子通过调节癌症相关基因或信号通路的表达和活性，促进消化系统癌症的发病机制。目前，几种靶向KATs、KDACs和BRDs的抑制剂正处于临床前试验阶段，并已显示出抗癌作用。消化道癌症包括食管癌、胃癌、结直肠癌、肝癌和胰腺癌，是一组异质性恶性肿瘤。然而，由于缺乏早期症状，这些癌症通常在晚期才被诊断出来，因此5年生存率较低。因此，迫切需要鉴定用于早期检测的新型生物标志物，以及准确预测临床结果并确定这些恶性肿瘤的有效治疗靶点。尽管赖氨酸乙酰化在消化道癌症中的作用仍不清楚，但进一步分析可能会加深我们对其在消化道癌症发病机制中作用的理解。本综述旨在总结赖氨酸乙酰化失调在消化道癌症中的影响和致病机制，以及其潜在的临床应用。
