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Scientific Reports

Scientific Reports

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AEG-1 silencing attenuates M2-polarization of glioma-associated microglia/macrophages and sensitizes glioma cells to temozolomide

Published:30 August 2021 DOI: 10.1038/s41598-021-96647-3 PMID: 34462446
Jing Li, Yuchen Sun, Xuanzi Sun, Xu Zhao, Yuan Ma, Yuzhu Wang, Xiaozhi Zhang

Abstract

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.

Substances (6)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Temozolomide 85622-93-1 C6H6N6O2 701 suppliers $5.00-$1310.00
Temozolomide 85622-93-1 C6H6N6O2 701 suppliers $5.00-$1310.00
Temozolomide 85622-93-1 C6H6N6O2 701 suppliers $5.00-$1310.00
Temozolomide 85622-93-1 C6H6N6O2 701 suppliers $5.00-$1310.00
85622-93-1 85622-93-1 C6H6N6O2 1 suppliers Inquiry
85622-93-1 85622-93-1 C6H6N6O2 1 suppliers Inquiry

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