Furthermore, we found that the protein level of IGF2BP3 was dramatically increased (Fig. 5D), while its level of ubiquitination was obviously decreased, in HECTD4-knockdown GBM cells (Fig. 5E), indicating that HECTD4 acts as an E3 ubiquitin ligase to degrade IGF2BP3 via the ubiquitin–proteasome pathway in glioma. This evidence concerns the gene IGF2BP3 and central nervous system cancer.