To explore how the ubiquitin-conjugating enzyme E2D3 (UBE2D3) influences temozolomide (TMZ) resistance in glioblastoma (GBM), and to clarify the association between UBE2D3 and WTAP. The UBE2D3 protein expression in GBM tissues were detected using immunohistochemistry (IHC) through tissue microarrays. The potential pathways of UBE2D3 in TCGA-GBM were predicted via Gene Set Enrichment Analysis (GSEA). To investigate UBE2D3's role in TMZ resistance, GBM cells were transduced with UBE2D3 shRNA or overexpression lentivirus, followed by assessments of CCK-8, flow cytometry, comet assay, and western blot analysis. Furthermore, a subcutaneous tumor model was established in nude mice using U87 cells transduced with interfering lentivirus to observe tumor growth and assess cell apoptosis using TUNEL staining. Mechanically, m