NSUN2 Promotes Prostate Cancer Cell Proliferation and Migration Through m5C Modifications of YES1

Prostate cancer (PCa) is one of the most common genitourinary malignancies in men worldwide. As a 5-methylcytosine (m5C) methyltransferase, NSUN2 has been implicated in regulating PCa progression. This study aimed to investigate the role of NSUN2 in PCa and elucidate its underlying mechanisms. The biological behaviors of PCa cells were assessed using Cell Counting Kit-8, EdU incorporation, and Transwell assays. The expression levels of relevant RNAs were determined via quantitative real-time PCR. The interaction between NSUN2 and YES proto-oncogene 1 (YES1) was examined through methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), and dual-luciferase reporter assays. Results showed that NSUN2 was elevated in PCa, and its downregulation suppressed cell viability, proliferation, migration, and invasion. Mechanistically, NSUN2 interacted with YES1 and stabilized its mRNA by promoting m5C modification on YES1. The oncogenic role of NSUN2 was further confirmed in xenograft models in vivo. In conclusion, our study demonstrated that NSUN2 facilitated malignant proliferation and migration of PCa cells by enhancing YES1 mRNA stability via m5C modification. These findings suggested that both NSUN2 and YES1 may serve as potential therapeutic targets for PCa, offering new strategies for treatment.