PRMT3, a type I protein arginine methyltransferase, is crucial in biology, especially in cancer. It catalyzes the mono-methylation and asymmetric di-methylation of histone and non-histone substrates, regulating various cellular functions [5]. It is involved in multiple pathways such as retinoic acid signaling [6], glycolytic metabolism [2], and cGAS/STING signaling [4].

In various cancers, PRMT3 has been shown to play significant roles. In hepatocellular carcinoma, PRMT3-mediated arginine methylation of IGF2BP1 promotes oxaliplatin resistance, and its overexpression can be a biomarker for this resistance [1]. In glioblastoma, knockdown of PRMT3 in cell lines and patient-derived glioblastoma stem cells reduced proliferation and migration, and inhibited tumor growth in xenograft mouse models, indicating that PRMT3 promotes glioblastoma progression via enhancing HIF1A-mediated glycolysis [2]. In endometrial carcinoma, inhibition of PRMT3 enhances the susceptibility of EC cells to ferroptosis, and blocking PRMT3 improves tumor suppression in response to cisplatin and radiation therapy [3]. In hepatocellular carcinoma, hepatocyte-specific knockout of Prmt3 suppressed HCC progression, and knockout in HCC cells increased CD8+ T cell infiltration, suggesting that PRMT3 drives PD-L1-mediated immune escape through activating PDHK1-regulated glycolysis [7]. In invasive micropapillary carcinoma of the breast, overexpression of PRMT3 was an independent risk factor for poor prognosis, and treatment with a PRMT3 inhibitor decreased xenograft tumorigenic capacity [8].

In conclusion, PRMT3 is a key regulator in multiple biological processes and disease conditions, especially in various cancers. Gene knockout and conditional knockout mouse models have been instrumental in revealing its role in promoting tumor progression, treatment resistance, and immune escape in different cancer types, providing potential therapeutic targets for these diseases.