Chair and Department of Biochemistry and Molecular Biology, Medical University of Lublin, Witolda Chodźki 1 St., 20-093 Lublin, Poland.
Independent Medical Biology Unit, Medical University of Lublin, Kazimierza Jaczewskiego 8b St., 20-090 Lublin, Poland.
Int J Mol Sci. 2021 Oct 30;22(21):11810. doi: 10.3390/ijms222111810.
Reversible Nε-lysine acetylation/deacetylation is one of the most common post-translational modifications (PTM) of histones and non-histone proteins that is regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). This epigenetic process is highly involved in carcinogenesis, affecting histone and non-histone proteins' properties and their biological functions. Some of the transcription factors, including tumor suppressors and oncoproteins, undergo this modification altering different cell signaling pathways. HDACs deacetylate their targets, which leads to either the upregulation or downregulation of proteins involved in the regulation of cell cycle and apoptosis, ultimately influencing tumor growth, invasion, and drug resistance. Therefore, epigenetic modifications are of great clinical importance and may constitute a new therapeutic target in cancer treatment. This review is aimed to present the significance of HDACs in carcinogenesis through their influence on functions of transcription factors, and therefore regulation of different signaling pathways, cancer progression, and metastasis.
组蛋白和非组蛋白的 Nε-赖氨酸可逆乙酰化/去乙酰化是最常见的翻译后修饰(PTM)之一,由组蛋白乙酰转移酶(HATs)和组蛋白去乙酰化酶(HDACs)调控。该表观遗传过程与癌症的发生密切相关,影响组蛋白和非组蛋白的性质及其生物学功能。一些转录因子,包括肿瘤抑制因子和癌蛋白,经历这种修饰,改变不同的细胞信号通路。HDACs 去乙酰化其靶标,导致参与细胞周期和细胞凋亡调节的蛋白质的上调或下调,最终影响肿瘤的生长、侵袭和耐药性。因此,表观遗传修饰具有重要的临床意义,可能成为癌症治疗的新靶点。本综述旨在通过影响转录因子的功能,以及因此调控不同的信号通路、癌症进展和转移,来阐述 HDACs 在癌症发生中的重要意义。