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PRMT1是非小细胞肺癌上皮-间质转化的新型调节因子。

PRMT1 Is a Novel Regulator of Epithelial-Mesenchymal-Transition in Non-small Cell Lung Cancer.

作者信息

Avasarala Sreedevi, Van Scoyk Michelle, Karuppusamy Rathinam Manoj Kumar, Zerayesus Sereke, Zhao Xiangmin, Zhang Wei, Pergande Melissa R, Borgia Jeffrey A, DeGregori James, Port J David, Winn Robert A, Bikkavilli Rama Kamesh

机构信息

From the Division of Pulmonary, Critical Care, Sleep and Allergy, and.

the Department of Pediatrics, University of Illinois at Chicago, Chicago, Illinois 60612.

出版信息

J Biol Chem. 2015 May 22;290(21):13479-89. doi: 10.1074/jbc.M114.636050. Epub 2015 Apr 6.

Abstract

Protein arginine methyl transferase 1 (PRMT1) was shown to be up-regulated in cancers and important for cancer cell proliferation. However, the role of PRMT1 in lung cancer progression and metastasis remains incompletely understood. In the present study, we show that PRMT1 is an important regulator of epithelial-mesenchymal transition (EMT), cancer cell migration, and invasion, which are essential processes during cancer progression, and metastasis. Additionally, we have identified Twist1, a basic helix-loop-helix transcription factor and a well-known E-cadherin repressor, as a novel PRMT1 substrate. Taken together, we show that PRMT1 is a novel regulator of EMT and arginine 34 (Arg-34) methylation of Twist1 as a unique "methyl arginine mark" for active E-cadherin repression. Therefore, targeting PRMT1-mediated Twist1 methylation might represent a novel strategy for developing new anti-invasive/anti-metastatic drugs. Moreover, methylated Twist1 (Arg-34), as such, could also emerge as a potential important biomarker for lung cancer.

摘要

蛋白质精氨酸甲基转移酶1(PRMT1)在癌症中呈上调表达,对癌细胞增殖至关重要。然而,PRMT1在肺癌进展和转移中的作用仍未完全明确。在本研究中,我们发现PRMT1是上皮-间质转化(EMT)、癌细胞迁移和侵袭的重要调节因子,而这些过程是癌症进展和转移过程中的关键环节。此外,我们还确定了Twist1,一种碱性螺旋-环-螺旋转录因子和著名的E-钙黏蛋白抑制因子,是PRMT1的一种新底物。综上所述,我们表明PRMT1是EMT的新型调节因子,Twist1的精氨酸34(Arg-34)甲基化是活性E-钙黏蛋白抑制的独特“甲基精氨酸标记”。因此,靶向PRMT1介导的Twist1甲基化可能代表一种开发新型抗侵袭/抗转移药物的新策略。此外,甲基化的Twist1(Arg-34)也可能成为肺癌潜在的重要生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03e7/4505594/3a85b130169a/zbc0251516970001.jpg

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