In conclusion, MSC-AS1 suppression degraded CPEB4 expression by sponging miR-373-3p, thereby suppressing cell viability, IC50 value of TMZ, proliferation, TMZ resistance, and elevating apoptosis in TMZ-resistant glioma cells in vitro and in vivo via PI3K/Akt pathway, indicating that MSC-AS1 might be a prognostic marker in TMZ-based glioma chemotherapy. This evidence concerns the gene CPEB4 and glioma.