METTL3 promotes prostate cancer cell metastasis and EMT by mediating NUP210 m6A modification.

[BACKGROUND] Prostate cancer (PCa) is an age-related epithelial malignancy with high metastatic potential. Although nucleoporin 210 (NUP210) is implicated in tumor progression, its role and mechanism in PCa metastasis remain unexplored.

[METHODS] Bioinformatics analysis (Gene Expression Omnibus (GEO)/The University of Alabama at Birmingham CANcer data analysis Portal (UALCAN) databases) and experimental validation (quantitative real-time PCR (qRT-PCR) and western blot) were applied to assess the expression of NUP210, methyltransferase-like 3 (METTL3), metastasis-related markers, and epithelial-mesenchymal transition (EMT)-related markers. Functional assays (transwell, in vivo metastasis models) and mechanistic studies (methylated RNA immunoprecipitation (MeRIP), RNA binding protein immunoprecipitation (RIP), and mRNA stability assays) were performed to elucidate the METTL3/NUP210 axis.

[RESULTS] NUP210 and METTL3 were highly expressed in PCa tissues and cells. Knockdown of NUP210 significantly inhibited PCa metastasis and EMT. Also, the animal study revealed that NUP210 silencing could inhibit the lung metastasis of PCa in vivo. METTL3-mediated N6-methyladenosine (m6A) modification stabilized NUP210 mRNA, and rescue experiments confirmed that NUP210 overexpression reversed the inhibitory effects of METTL3 silencing on PCa cell metastasis and EMT.

[CONCLUSION] The METTL3-mediated m6A modification of NUP210 may promote PCa metastasis and EMT. This newly identified METTL3/NUP210 axis deepens the understanding of PCa progression and suggests its potential for further therapeutic exploration.