摘要：Glioma is the most frequent primary malignancy in the brain; temozolomide (TMZ) is the first-line chemotherapeutic agent used to combat this tumor. We showed here that astrocyte elevated gene-1 (
AEG-1) was overexpressed in glioma tissues and associated with a worse subtype and a poor prognosis. CCK-8 proliferation assays and clone formation experiments presented that
AEG-1 knockdown sensitizes glioma cells to TMZ. The
γH2AX foci formation assays indicated that
AEG-1 silencing promotes TMZ-induced DNA damage in glioma cells. Glioma-associated microglia/macrophages (GAMs), the largest subpopulation infiltrating glioma, play important roles in the tumor microenvironment. Bioinformatics analyses and functional studies demonstrated that
AEG-1 silencing decreased M2-polarization of HMC3 microglia and the secretion of tumor supportive cytokines
IL-6 and
TGF-β1. The expression of
AEG-1 was positively associated with M2 markers in glioma tissues varified by IHC staining. Based on the results of Affymetrix microarray and GSEA analyses, Western blot and Co-Immunoprecipitation assays were conducted to show that
AEG-1 activates Wnt/β-catenin signaling by directly interacting with
GSK-3β. The co-localization of
AEG-1 and
GSK-3β in the cytoplasm of glioma cells was detected through immunofluorescence staining. This study raises the possibility that targeting
AEG-1 might improve the efficiency of chemotherapy and reduce immunosuppressive M2 GAMs in glioma.
