精氨酸甲基转移酶抑制剂1通过下调真核翻译起始因子4E（eIF4E）并靶向蛋白精氨酸甲基转移酶5（PRMT5）来抑制胃癌。
Arginine methyltransferase inhibitor 1 inhibits gastric cancer by downregulating eIF4E and targeting PRMT5.
作者信息
Zhang Baolai, Zhang Su, Zhu Lijuan, Chen Xue, Zhao Yunfeng, Chao Li, Zhou Juanping, Wang Xing, Zhang Xinyang, Ma Nengqian
机构信息
Department of Pharmacology, School of Basic Medical Sciences, Lanzhou University, Key Lab of Preclinical Study for New Drugs of Gansu Province, Lanzhou, PR China.
Department of Pharmacology, School of Basic Medical Sciences, Lanzhou University, Key Lab of Preclinical Study for New Drugs of Gansu Province, Lanzhou, PR China.
出版信息
Toxicol Appl Pharmacol. 2017 Dec 1;336:1-7. doi: 10.1016/j.taap.2017.10.002. Epub 2017 Oct 4.
Arginine methylation is carried out by protein arginine methyltransferase (PRMTs) family. Arginine methyltransferase inhibitor 1 (AMI-1) is mainly used to inhibit type I PRMT activity in vitro. However, the effects of AMI-1 on type II PRMT5 activity and gastric cancer (GC) remain unclear. In this study, we provided the first evidence that AMI-1 significantly inhibited GC cell proliferation and migration while induced GC cell apoptosis, and reduced the expression of PRMT5, eukaryotic translation initiation factor 4E (eIF4E), symmetric dimethylation of histone 3 (H3R8me2s) and histone 4 (H4R3me2s). In addition, AMI-1 inhibited tumor growth, downregulated eIF4E, H4R3me2s and H3R8me2s expression in mice xenografts model of GC. Collectively, our results suggest that AMI-1 inhibits GC by downregulating eIF4E and targeting type II PRMT5.
精氨酸甲基化由蛋白质精氨酸甲基转移酶（PRMTs）家族完成。精氨酸甲基转移酶抑制剂1（AMI-1）主要用于在体外抑制I型PRMT活性。然而，AMI-1对II型PRMT5活性和胃癌（GC）的影响仍不清楚。在本研究中，我们首次证明AMI-1显著抑制GC细胞增殖和迁移，同时诱导GC细胞凋亡，并降低PRMT5、真核翻译起始因子4E（eIF4E）、组蛋白3对称二甲基化（H3R8me2s）和组蛋白4（H4R3me2s）的表达。此外，在GC小鼠异种移植模型中，AMI-1抑制肿瘤生长，下调eIF4E、H4R3me2s和H3R8me2s的表达。总体而言，我们的结果表明，AMI-1通过下调eIF4E和靶向II型PRMT5来抑制GC。
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