KEY TAKEAWAYS
- The study aimed to investigate the role and mechanism of IGF2BP2 in promoting M2 macrophage polarization and BCa progression.
- Researchers noticed that IGF2BP2 significantly enhances M2 macrophage polarization and BCa progression by stabilizing NRP1 mRNA.
Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) has been confirmed to play an oncogenic role in many cancers. However, the role and mechanism of IGF2BP2 in bladder cancer (BCa) still deserve to be further revealed.
Dian Fu and the team aimed to assess the influence of IGF2BP2 on BCa progression through its interaction with NRP1 mRNA and its role in M2 macrophage polarization.
They performed an inclusive analysis to investigate the role of IGF2BP2 and neuronilin-1 (NRP1) in BCa. The study measured the mRNA and protein levels of IGF2BP2 and NRP1 using real-time quantitative PCR (RT-qPCR) and western blot techniques.
To assess cell proliferation, apoptosis, migration, and invasion, colony formation assays, EdU assays, CCK8 assays, flow cytometry, and transwell assays were conducted. Additionally, a xenograft tumor model was utilized to evaluate the role of IGF2BP2 in vivo.
Patients’ BCa cells were co-cultured with THP-1-M0 macrophages using the conditioned medium (CM) to induce macrophage polarization. The polarization of M2 macrophages was assessed by detecting the mRNA levels of M2 macrophage markers using RT-qPCR and measuring the proportion of M2 macrophage markers using flow cytometry.
Furthermore, methylated RNA immunoprecipitation (MeRIP) and RNA immunoprecipitation (RIP) assays were performed to determine the m6A levels and to explore the interaction between IGF2BP2 and NRP1.
About IGF2BP2 and NRP1 were upregulated in BCa tissues and cells. IGF2BP2 knockdown suppressed BCa cell growth and metastasis, as well as inhibited BCa tumor growth. After THP-1-M0 macrophages were co-cultured with the CM of BCa cells, the levels of M2 macrophage markers were markedly enhanced, while this effect was abolished by IGF2BP2 knockdown.
IGF2BP2 level was positively correlated with NRP1 level, and it could increase NRP1 mRNA stability. NRP1 overexpression reversed the suppressive effect of IGF2BP2 knockdown on M2 macrophage polarization and BCa cell progression.
The study concluded that the m6A-reader IGF2BP2 enhances M2 macrophage polarization and BCa cell progression by promoting the stability of NRP1 mRNA. These findings suggest that IGF2BP2 plays a crucial role in the tumor microenvironment and could be a potential therapeutic target for BCa treatment.
The study received no funds.
Source: https://pubmed.ncbi.nlm.nih.gov/39014364/
Fu D, Shi X, Yi X, et al. (2024). “m6A reader IGF2BP2 promotes M2 macrophage polarization and malignant biological behavior of bladder cancer by stabilizing NRP1 mRNA expression.” BMC Urol. 2024 Jul 16;24(1):147. doi: 10.1186/s12894-024-01534-4. PMID: 39014364; PMCID: PMC11251312.
