In gliomas, Pan et al. found that circNEIL3 interacts with IGF2BP in the cytoplasm, enhancing the stability of IGF2BP3 protein and inhibiting the E3 ubiquitin ligase HECTD4-mediated degradation of IGF2BP3 at the post-transcriptional level to promote the polarization of macrophage toward an immunosuppressive phenotype enabling gliomas to acquire angiogenic and immunosuppressive properties in turn promoting tumor progression. Here, HECTD4 is linked to central nervous system cancer.