CARM1是一种精氨酸甲基转移酶，可以进行翻译后修饰，调控多个水平的RNA产生和加工。它的底物包括组蛋白、转录因子、转录共激活因子和剪接因子等。CARM1在许多不同类型的癌症中过度表达，并且常常促进作为转化细胞状态驱动因子的转录因子程序，这个过程被称为转录因子依赖性。针对这些致癌转录因子途径是困难的，但可以通过消除它们依赖的关键共激活因子的活性来解决。CARM1广泛表达，并且其基因敲除对胚胎发育的影响较精氨酸甲基转移酶PRMT1和PRMT5的基因缺失要小，这表明靶向CARM1可能具有良好的耐受性。在这里，我们将总结从小鼠研究中获得的CARM1的正常体内功能，扩展由CARM1调控的转录途径，并强调最近在不同生物环境中鉴定CARM1的致癌特性的研究。本综述旨在引发对开发针对CARM1的人类药物治疗的兴趣，因为目前尚无用于临床试验的CARM1抑制剂。版权所有 © 2023 作者。由Elsevier Inc.出版。保留所有权利。

CARM1 is an arginine methyltransferase that post-translationally modifies proteins that regulate multiple levels of RNA production and processing. Its substrates include histones, transcription factors, co-regulators of transcription and splicing factors. CARM1 is overexpressed in many different cancer types, and often promotes transcription factor programs that are co-opted as drivers of the transformed cell state, a process known as transcription factor addiction. Targeting these oncogenic transcription factor pathways is difficult but could be addressed by removing the activity of the key coactivators on which they rely. CARM1 is ubiquitously expressed, and its knockout is less detrimental in embryonic development than deletion of the arginine methyltransferases PRMT1 and PRMT5, suggesting that therapeutic targeting of CARM1 may be well tolerated. Here, we will summarize the normal in vivo functions of CARM1 that have been gleaned from mouse studies, expand on the transcriptional pathways that are regulated by CARM1, and finally highlight recent studies that have identified oncogenic properties of CARM1 in different biological settings. This review is meant to kindle an interest in the development of human drug therapies targeting CARM1, as there are currently no CARM1 inhibitors available for use in clinical trials.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.