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精氨酸甲基转移酶 1 在神经胶质瘤发生中的作用。

The role of protein arginine-methyltransferase 1 in gliomagenesis.

机构信息

The National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.

出版信息

BMB Rep. 2012 Aug;45(8):470-5. doi: 10.5483/BMBRep.2012.45.8.022.

Abstract

Protein arginine methyltransferase 1 (PRMT1), a type-I arginine methyltransferase, has been implicated in diverse cellular events. We have focused on the role of PRMT1 in gliomagenesis. In this study, we showed that PRMT1 expression was up-regulated in glioma tissues and cell lines compared with normal brain tissues. The knock-down of PRMT1 resulted in an arrest in the G1-S phase of the cell cycle, proliferation inhibition and apoptosis induction in four glioma cell lines (T98G, U87MG, U251, and A172). Moreover, an in vivo study confirmed that the tumor growth in nude mouse xenografts was significantly decreased in the RNAi-PRMT1 group. Additionally, we found that the level of the asymmetric dimethylated modification of H4R3, a substrate of PRMT1, was higher in glioma cells than in normal brain tissues and decreased after PRMT1 knock-down. Our data suggest a potential role for PRMT1 as a novel biomarker of and therapeutic target in gliomas.

摘要

精氨酸甲基转移酶 1(PRMT1)是一种 I 型精氨酸甲基转移酶,参与多种细胞事件。我们专注于 PRMT1 在神经胶质瘤发生中的作用。在这项研究中,我们发现与正常脑组织相比,PRMT1 在神经胶质瘤组织和细胞系中表达上调。在四种神经胶质瘤细胞系(T98G、U87MG、U251 和 A172)中,敲低 PRMT1 导致细胞周期 G1-S 期停滞、增殖抑制和凋亡诱导。此外,体内研究证实,在 RNAi-PRMT1 组中,裸鼠异种移植瘤的生长明显减少。此外,我们发现 PRMT1 的底物 H4R3 的不对称二甲基化修饰水平在神经胶质瘤细胞中高于正常脑组织,并且在敲低 PRMT1 后降低。我们的数据表明 PRMT1 作为神经胶质瘤的新型生物标志物和治疗靶点具有潜在作用。

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