Ang Gareth Chin Khye, Gupta Amogh, Surana Uttam, Yap Shirlyn Xue Ling, Taneja Reshma
Healthy Longevity Translational Research Program, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Singapore.
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Singapore.
Cancers (Basel). 2022 Jun 9;14(12):2855. doi: 10.3390/cancers14122855.
Euchromatin histone lysine methyltransferases (EHMTs) are epigenetic regulators responsible for silencing gene transcription by catalyzing H3K9 dimethylation. Dysregulation of EHMT1/2 has been reported in multiple cancers and is associated with poor clinical outcomes. Although substantial insights have been gleaned into the downstream targets and pathways regulated by EHMT1/2, few studies have uncovered mechanisms responsible for their dysregulated expression. Moreover, EHMT1/2 interacting partners, which can influence their function and, therefore, the expression of target genes, have not been extensively explored. As none of the currently available EHMT inhibitors have made it past clinical trials, understanding upstream regulators and EHMT protein complexes may provide unique insights into novel therapeutic avenues in EHMT-overexpressing cancers. Here, we review our current understanding of the regulators and interacting partners of EHMTs. We also discuss available therapeutic drugs that target the upstream regulators and binding partners of EHMTs and could potentially modulate EHMT function in cancer progression.
常染色质组蛋白赖氨酸甲基转移酶（EHMTs）是表观遗传调控因子，负责通过催化H3K9二甲基化使基因转录沉默。已有报道称EHMT1/2在多种癌症中失调，并与不良临床结果相关。尽管已经对EHMT1/2调控的下游靶点和通路有了大量深入了解，但很少有研究揭示其表达失调的机制。此外，尚未广泛探索能够影响EHMT1/2功能进而影响靶基因表达的相互作用蛋白。由于目前可用的EHMT抑制剂均未通过临床试验，了解上游调节因子和EHMT蛋白复合物可能为过表达EHMT的癌症的新治疗途径提供独特见解。在此，我们综述了目前对EHMTs调节因子和相互作用蛋白的认识。我们还讨论了针对EHMTs上游调节因子和结合蛋白的可用治疗药物，这些药物可能在癌症进展中调节EHMT功能。
