Protein arginine methyltransferases (PRMTs): Orchestrators of cancer pathogenesis, immunotherapy dynamics, and drug resistance

甲基转移酶 表观遗传学 癌症 癌变 蛋白质精氨酸甲基转移酶5 组蛋白 染色质 生物 癌症研究 甲基化 遗传学 基因
作者
Yihang Gao,Chongchong Feng,Jingru Ma,Qingzhu Yan
出处
期刊:Biochemical Pharmacology [Elsevier BV]
卷期号:221: 116048-116048 被引量:21
标识
DOI:10.1016/j.bcp.2024.116048
摘要

Protein Arginine Methyltransferases (PRMTs) are a family of enzymes regulating protein arginine methylation, which is a post-translational modification crucial for various cellular processes. Recent studies have highlighted the mechanistic role of PRMTs in cancer pathogenesis, immunotherapy, and drug resistance. PRMTs are involved in diverse oncogenic processes, including cell proliferation, apoptosis, and metastasis. They exert their effects by methylation of histones, transcription factors, and other regulatory proteins, resulting in altered gene expression patterns. PRMT-mediated histone methylation can lead to aberrant chromatin remodeling and epigenetic changes that drive oncogenesis. Additionally, PRMTs can directly interact with key signaling pathways involved in cancer progression, such as the PI3K/Akt and MAPK pathways, thereby modulating cell survival and proliferation. In the context of cancer immunotherapy, PRMTs have emerged as critical regulators of immune responses. They modulate immune checkpoint molecules, including programmed cell death protein 1 (PD-1), through arginine methylation. Drug resistance is a significant challenge in cancer treatment, and PRMTs have been implicated in this phenomenon. PRMTs can contribute to drug resistance through multiple mechanisms, including the epigenetic regulation of drug efflux pumps, altered DNA damage repair, and modulation of cell survival pathways. In conclusion, PRMTs play critical roles in cancer pathogenesis, immunotherapy, and drug resistance. In this overview, we have endeavored to illuminate the mechanistic intricacies of PRMT-mediated processes. Shedding light on these aspects will offer valuable insights into the fundamental biology of cancer and establish PRMTs as promising therapeutic targets.
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