Srivastava Rashmi, Singh Rubi, Jauhari Shaurya, Lodhi Niraj, Srivastava Rakesh
Department of Zoology, Babasaheb Bhimrao Ambedkar University, Lucknow 226025, Uttar Pradesh, India.
Department of Hematology, Bioreference Laboratories, Elmwood Park, NJ 07407, USA.
Epigenomes. 2023 May 17;7(2):10. doi: 10.3390/epigenomes7020010.
Epigenetic modifications are heritable, reversible changes in histones or the DNA that control gene functions, being exogenous to the genomic sequence itself. Human diseases, particularly cancer, are frequently connected to epigenetic dysregulations. One of them is histone methylation, which is a dynamically reversible and synchronously regulated process that orchestrates the three-dimensional epigenome, nuclear processes of transcription, DNA repair, cell cycle, and epigenetic functions, by adding or removing methylation groups to histones. Over the past few years, reversible histone methylation has become recognized as a crucial regulatory mechanism for the epigenome. With the development of numerous medications that target epigenetic regulators, epigenome-targeted therapy has been used in the treatment of malignancies and has shown meaningful therapeutic potential in preclinical and clinical trials. The present review focuses on the recent advances in our knowledge on the role of histone demethylases in tumor development and modulation, in emphasizing molecular mechanisms that control cancer cell progression. Finally, we emphasize current developments in the advent of new molecular inhibitors that target histone demethylases to regulate cancer progression.
表观遗传修饰是组蛋白或DNA中可遗传的、可逆的变化，这些变化控制着基因功能，且独立于基因组序列本身之外。人类疾病，尤其是癌症，常常与表观遗传失调有关。其中之一是组蛋白甲基化，它是一个动态可逆且同步调控的过程，通过向组蛋白添加或去除甲基基团来协调三维表观基因组、转录、DNA修复、细胞周期和表观遗传功能等核过程。在过去几年中，可逆性组蛋白甲基化已被公认为表观基因组的关键调控机制。随着众多靶向表观遗传调节剂药物的开发，表观基因组靶向治疗已被用于恶性肿瘤的治疗，并在临床前和临床试验中显示出有意义的治疗潜力。本综述重点关注我们对组蛋白去甲基化酶在肿瘤发生和调控中的作用的最新认识进展，强调控制癌细胞进展的分子机制。最后，我们着重介绍靶向组蛋白去甲基化酶以调节癌症进展的新型分子抑制剂的最新进展。
