Protein arginine methyltransferase crosstalk: decoding the synergistic-antagonistic axis in cancer therapy

Protein arginine methyltransferases (PRMTs) are abnormally expressed in various tumors and participate in multiple tumorigenic processes, including proliferation, metastasis, drug resistance, and metabolic reprogramming. However, in recent years, with the in-depth exploration of the functions of PRMTs and their associated tumorigenic mechanisms, the complex crosstalk relationships among different PRMTs have been increasingly highlighted. Different PRMTs may not only exhibit synergistic tumor-promoting effects but also demonstrate antagonistic effects in certain tumor biological functions. This makes the scientific and rational use of PRMT inhibitors a key factor for effective tumor suppression. The review aims to provide a comprehensive overview of the functional roles of different PRMTs in tumors, with a particular focus on their cross-functional regulatory mechanisms within the complex regulatory networks of tumors. Meanwhile, it summarizes the current research progress on PRMT inhibitors and elaborates on some limitations associated with PRMT-targeted therapy. Through the integration and analysis of existing research findings, this review offers a novel perspective on the complex regulatory roles of different PRMTs jointly participating in biological functions. Accumulating evidence suggests that implementing a multi-targeted intervention strategy for PRMTs and conducting stage-specific inhibition of PRMTs according to the progression stage of tumor development hold the potential to exert more significant therapeutic effects in the field of tumor treatment.