Dorna Dawid, Paluszczak Jarosław
Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, ul. Święcickiego 4, 60-781 Poznan, Poland.
Cells. 2022 Mar 17;11(6):1023. doi: 10.3390/cells11061023.
Epigenetic aberrations, associated with altered DNA methylation profiles and global changes in the level of histone modifications, are commonly detected in head and neck squamous cell carcinomas (HNSCC). Recently, histone lysine demethylases have been implicated in the pathogenesis of HNSCC and emerged as potential molecular targets. Histone lysine demethylases (KDMs) catalyze the removal of methyl groups from lysine residues in histones. By affecting the methylation of H3K4, H3K9, H3K27, or H3K36, these enzymes take part in transcriptional regulation, which may result in changes in the level of expression of tumor suppressor genes and protooncogenes. KDMs are involved in many biological processes, including cell cycle control, senescence, DNA damage response, and heterochromatin formation. They are also important regulators of pluripotency. The overexpression of most KDMs has been observed in HNSCC, and their inhibition affects cell proliferation, apoptosis, cell motility, invasiveness, and stemness. Of all KDMs, KDM1, KDM4, KDM5, and KDM6 proteins are currently regarded as the most promising prognostic and therapeutic targets in head and neck cancers. The aim of this review is to present up-to-date knowledge on the significance of histone lysine demethylases in head and neck carcinogenesis and to discuss the possibility of using them as prognostic markers and pharmacological targets in patients' treatment.
表观遗传畸变与DNA甲基化谱改变及组蛋白修饰水平的整体变化相关，在头颈部鳞状细胞癌（HNSCC）中普遍存在。最近，组蛋白赖氨酸去甲基化酶与HNSCC的发病机制有关，并成为潜在的分子靶点。组蛋白赖氨酸去甲基化酶（KDMs）催化从组蛋白赖氨酸残基上去除甲基基团。通过影响H3K4、H3K9、H3K27或H3K36的甲基化，这些酶参与转录调控，这可能导致肿瘤抑制基因和原癌基因表达水平的变化。KDMs参与许多生物学过程，包括细胞周期控制、衰老、DNA损伤反应和异染色质形成。它们也是多能性的重要调节因子。在HNSCC中已观察到大多数KDMs的过表达，抑制它们会影响细胞增殖、凋亡、细胞运动、侵袭性和干性。在所有KDMs中，KDM1、KDM4、KDM5和KDM6蛋白目前被认为是头颈部癌症中最有前景的预后和治疗靶点。本综述的目的是介绍关于组蛋白赖氨酸去甲基化酶在头颈部癌变中的意义的最新知识，并讨论将它们用作患者治疗中的预后标志物和药理学靶点的可能性。
