Concurrent chemotherapy is the standard treatment strategy for advanced-stage nasopharyngeal carcinoma (NPC). However, chemoresistance inevitable develops and the underlying mechanism remains poorly understood. In this study, we identify the arginine methyltransferase PRMT5 as a key gene associated with chemoresistance to paclitaxel in NPC. We demonstrate that PRMT5 facilitated paclitaxel resistance by inducing KCNMB4 expression in nasopharyngeal carcinoma cells. Mechanistically, PRMT5 is recruited to the promoter region of KCNMB4, where it catalyzes H3R2me2s and enhances KCNMB4 expression. Furthermore, elevated levels of PRMT5 or KCNMB4 correlated with poorer survival and higher recurrence rates in NPC patients. Notably, genetic or pharmacological inhibition of PRMT5 significantly sensitized NPC cells to paclitaxel, both in vitro and in vivo. Collectively, these results suggest that the PRMT5-KCNMB4 axis plays a crucial role in mediating chemoresistance in NPC and targeting this axis may provide a promising therapeutic strategy for late-stage NPC patients.
© 2025. The Author(s).