The following is a summary of “m6A reader IGF2BP2 promotes M2 macrophage polarization and malignant biological behavior of bladder cancer by stabilizing NRP1 mRNA expression,” published in the July 2024 issue of Urology by Fu et al.

Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) has been established as an oncogene in various cancers, yet its role and mechanism in bladder cancer (BCa) warrant further investigation. This study aims to elucidate the function of IGF2BP2 in BCa and its influence on tumor progression and macrophage polarization. The mRNA and protein expressions of IGF2BP2 and neuronilin-1 (NRP1) were quantified using real-time quantitative PCR (RT-qPCR) and western blotting. 

Functional assays, including colony formation, EdU incorporation, CCK8 proliferation, flow cytometry, and transwell migration and invasion assays, were utilized to assess the impact of IGF2BP2 on BCa cell behaviors. Additionally, a xenograft tumor model was employed to validate the in vivo role of IGF2BP2. To investigate macrophage polarization, THP-1-derived M0 macrophages were co-cultured with conditioned medium (CM) from BCa cells, and M2 macrophage markers were analyzed using RT-qPCR and flow cytometry to investigate macrophage polarization. The interaction between IGF2BP2 and NRP1 mRNA and m6A modification levels was examined through methylated RNA immunoprecipitation (MeRIP) and RNA immunoprecipitation (RIP) assays. 

Results demonstrated that IGF2BP2 and NRP1 were significantly upregulated in BCa tissues and cell lines. Silencing IGF2BP2 suppressed BCa cell proliferation, migration, invasion, and tumor growth. Co-culturing THP-1-M0 macrophages with BCa CM significantly enhanced M2 macrophage marker levels, an effect negated by IGF2BP2 knockdown. IGF2BP2 expression positively correlated with NRP1 levels and enhanced NRP1 mRNA stability. Furthermore, NRP1 overexpression reversed the inhibitory effects of IGF2BP2 knockdown on M2 macrophage polarization and BCa cell progression. 

In conclusion, the m6A reader IGF2BP2 facilitates M2 macrophage polarization and promotes the malignant behavior of BCa cells by stabilizing NRP1 mRNA. These findings highlight the IGF2BP2-NRP1 axis as a potential therapeutic target in bladder cancer, offering new insights into the molecular mechanisms driving BCa progression.

Source: bmcurol.biomedcentral.com/articles/10.1186/s12894-024-01534-4