Functional rescue experiments also showed that CUL2 knockdown increased the proliferation, migration and invasion abilities of GBM cells, which could be reversed by RPN2 downregulation (Figure S4J- K), indicating that CUL2 could act as a ubiquitin ligase of RPN2 to regulate the malignant progression of GBM. The gene discussed is RPN2; the disease is glioblastoma.