Targeting the PRMT1 axis in cancer: from epigenetic plasticity to contextual therapeutic interventions

Abstract

Protein arginine methyltransferase 1 (PRMT1), the predominant Type I arginine methyltransferase, is reported to play the key role in regulating cancer epigenetics. Its activity directs gene expression, chromatin structure and transcriptional activation by mediating asymmetric dimethylation of histone and non-histone proteins. Despite extensive characterization of PRMT1 as a dominant arginine methyltransferase, its paradoxical oncogenic and tumor-suppressive roles have remained conceptually fragmented. This review integrates isoform-specific biology, chromatin crosstalk, and emerging therapeutic strategies to resolve this paradox and provide a translational framework for PRMT1-targeted precision oncology. PRMT1 exhibits context-dependent activity. While it predominantly functions as an oncogenic regulator in both solid tumors and hematological malignancies, emerging evidence indicates that PRMT1 may also exert tumor-suppressive effects under specific metabolic, apoptotic, and microenvironmental contexts. This differential behavior is mediated by chromatin remodeling, transcription factor recruitment, enhancer-promoter interactions, and its interplay with key epigenetic regulators such as EZH2, leukemogenic fusion proteins like MLL-AF9, and non-coding RNAs. As a drug target, PRMT1 has gained significant attention, with several small-molecule inhibitors demonstrating efficacy in preclinical and early clinical studies. However, challenges such as off-target effects and resistance highlight the need for a deeper mechanistic understanding of its cancer-specific roles. By synthesizing current insights, this review elucidates PRMT1’s multifaceted role in cancer biology and underscores its potential as a target for precision oncology, laying the groundwork for future therapeutic strategies.