# PRMT5 upregulates KCNMB4 expression via histone methylation to promote paclitaxel resistance in advanced nasopharyngeal carcinoma

## TL;DR

This study shows that PRMT5 promotes paclitaxel resistance in nasopharyngeal cancer by increasing KCNMB4 expression, offering a potential new treatment target.

## Contribution

The study identifies PRMT5 as a novel driver of paclitaxel resistance via histone methylation of KCNMB4 in nasopharyngeal carcinoma.

## Key findings

- PRMT5 enhances paclitaxel resistance by upregulating KCNMB4 expression through histone methylation.
- High PRMT5 or KCNMB4 levels correlate with worse survival and higher recurrence in NPC patients.
- Inhibiting PRMT5 sensitizes NPC cells to paclitaxel in both lab and animal models.

## Abstract

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.