Prostate cancer remains a leading cause of mortality in men, particularly in advanced stages. Protein post-translational modifications play a crucial role in tumorigenesis and progression. PRMT1, an enzyme that mediates arginine methylation, has been implicated in cancer development across multiple tumor types. However, its role in prostate cancer growth remains unclear. This study aims to investigate how PRMT1-mediated arginine methylation contributes to prostate cancer progression and to identify potential therapeutic targets.

Immunohistochemistry on human prostate cancer tissues was conducted to evaluate the association between PRMT1 and tumor presence. Lentiviral vectors were utilized to establish PRMT1 overexpression and knockdown models in PC-3 and 22RV1 cell lines. Additionally, lentiviral vectors were used to generate PC-3 and 22RV1 models with PABPC1 R278 and R493 site-specific mutations. A subcutaneous tumor model was constructed in nude mice. In vitro studies with PC-3 and 22RV1 cells confirmed the PRMT1-associated phenotype. Mass spectrometry and co-immunoprecipitation assays identified potential PRMT1-binding proteins and modification sites. Mechanistic validation was conducted using qPCR and Western blot analyses, while in vivo experiments confirmed the phenotype.

Immunohistochemistry of human prostate cancer tissues revealed a positive correlation between PRMT1 expression and prostate cancer progression. Phenotypic studies in human prostate cancer cell lines 22RV1 and PC-3 indicated that PRMT1 is associated with prostate cancer growth and metastasis. In a subcutaneous tumor model in nude mice, PRMT1 overexpression was found to promote prostate cancer growth. Mass spectrometry and immunoprecipitation assays identified arginine dimethylation of PABPC1 at R278 and R493 as PRMT1-mediated modifications. Western blot and qPCR experiments showed that PRMT1-induced methylation of PABPC1 affected its protein stability, achieved through alterations in PABPC1 ubiquitination. Rescue experiments and the subcutaneous tumor model in nude mice further confirmed that PRMT1-mediated methylation of PABPC1 at R278 and R493 promotes prostate cancer progression.

We found that PRMT1-mediated arginine dimethylation of PABPC1 regulates its ubiquitination, thereby enhancing the stability of the PABPC1 protein and promoting prostate cancer progression.