de Korte Daphne, Hoekstra Menno
Division of Systems Pharmacology and Pharmacy, Leiden Academic Centre for Drug Research, Leiden University, Gorlaeus Laboratories, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Biomolecules. 2025 Jan 27;15(2):185. doi: 10.3390/biom15020185.
Protein arginine methyltransferase 1 (PRMT1) is the main PRMT family member involved in the formation of monomethylarginine and asymmetric dimethylarginine on its protein substrates. Many protein substrates of PRMT1 are key mediators of cell proliferation and oncogenesis. As such, the function of PRMT1 has been most prominently investigated in the context of cancer development. However, recent in vitro and in vivo studies have highlighted that PRMT1 may also promote metabolic disorders. With the current review, we aim to present an in-depth overview of how PRMT1 influences epigenetic modulation, transcriptional regulation, DNA damage repair, and signal transduction in cancer. Furthermore, we summarize the current knowledge regarding the role of PRMT1 in metabolic reprogramming, lipid metabolism, and glucose metabolism and describe the association of PRMT1 with numerous metabolic pathologies such as obesity, liver disease, and type 2 diabetes. It has become apparent that inhibiting the function of PRMT1 will likely serve as the most beneficial therapeutic approach, since several PRMT1 inhibitors have already been shown to exert positive effects on both cancer and metabolic disease in preclinical settings. However, pharmacological PRMT1 inhibition has not yet been shown to be therapeutically effective in clinical studies.
蛋白质精氨酸甲基转移酶1（PRMT1）是PRMT家族的主要成员，参与在其蛋白质底物上形成单甲基精氨酸和不对称二甲基精氨酸。PRMT1的许多蛋白质底物是细胞增殖和肿瘤发生的关键介质。因此，PRMT1的功能在癌症发展的背景下得到了最广泛的研究。然而，最近的体外和体内研究强调，PRMT1也可能促进代谢紊乱。在本综述中，我们旨在深入概述PRMT1如何影响癌症中的表观遗传调控、转录调控、DNA损伤修复和信号转导。此外，我们总结了目前关于PRMT1在代谢重编程、脂质代谢和葡萄糖代谢中的作用的知识，并描述了PRMT1与肥胖、肝病和2型糖尿病等多种代谢疾病的关联。显然，抑制PRMT1的功能可能是最有益的治疗方法，因为几种PRMT1抑制剂已在临床前研究中显示对癌症和代谢疾病均有积极作用。然而，在临床研究中，药理学上抑制PRMT1尚未显示出治疗效果。
