PRMT1 in human neoplasm: cancer biology and potential therapeutic target

Abstract

Protein arginine methyltransferase 1 (PRMT1), the predominant type I protein arginine methyltransferase, plays a crucial role in normal biological functions by catalyzing the methylation of arginine side chains, specifically monomethylarginine (MMA) and asymmetric dimethylarginine (ADMA), within proteins. Recent investigations have unveiled an association between dysregulated PRMT1 expression and the initiation and progression of tumors, significantly impacting patient prognosis, attributed to PRMT1’s involvement in regulating various facets of tumor cell biology, including DNA damage repair, transcriptional and translational regulation, as well as signal transduction. In this review, we present an overview of recent advancements in PRMT1 research across different tumor types, with a specific focus on its contributions to tumor cell proliferation, metastasis, invasion, and drug resistance. Additionally, we expound on the dynamic functions of PRMT1 during distinct stages of cancer progression, elucidating its unique regulatory mechanisms within the same signaling pathway and distinguishing between its promotive and inhibitory effects. Importantly, we sought to provide a comprehensive summary and analysis of recent research progress on PRMT1 in tumors, contributing to a deeper understanding of its role in tumorigenesis, development, and potential treatment strategies.

Oligomerization of protein arginine methyltransferase 1 and its effect on methyltransferase activity and substrate specificity

“…The PRMT family consists of nine members that are classified into three types (type I, II, or III), which are defined by whether the enzymes form monomethylated, asymmetric dimethylated, or symmetric dimethylated arginyl products (Morales et al, 2016 ; Tewary et al, 2019 ; Thiebaut et al, 2021 ). Protein arginine methylation of histone and non‐histone proteins is important in a wide range of cellular processes including the regulation of DNA transcription, DNA damage repair, RNA processing and translation, and protein stability; aberrant arginine methylation is implicated in cardiovascular, neuromuscular, neurodegenerative, lung and cancer disease states (Al‐Hamashi et al, 2020 ; Jarrold & Davies, 2019 ; Lorton & Shechter, 2019 ; Shen et al, 2024 ; Thiebaut et al, 2021 ; Xu & Richard, 2021 ), prompting a concerted effort to develop PRMT inhibitors (Dong et al, 2022 ; Hwang et al, 2021 ; Jarrold & Davies, 2019 ; Li et al, 2019 ; Shen et al, 2024 ).…”