title: MAGED4 expression in glioma and upregulation in glioma cell lines with 5-aza-2'-deoxycytidine treatment.
abstract: Melanoma-associated antigen (MAGE) family genes have been considered as potentially promising targets for anticancer immunotherapy. MAGED4 was originally identified as a glioma-specific antigen. Current knowledge about MAGED4 expression in glioma is only based on mRNA analysis and MAGED4 protein expression has not been elucidated. In the present study, we investigated this point and found that MAGED4 mRNA and protein were absent or very lowly expressed in various normal tissues and glioma cell line SHG44, but overexpressed in glioma cell lines A172,U251,U87-MG as well as glioma tissues, with significant heterogeneity. Furthermore, MAGED4 protein expression was positively correlated with the glioma type and grade. We also found that the expression of MAGED4 inversely correlated with the overall methylation status of the MAGED4 promoter CpG island. Furthermore, when SHG44 and A172 with higher methylation were treated with the DNA demethylating agent 5-aza-2'-deoxycytidine (5-AZA-CdR) reactivation of MAGED4 mRNA was mediated by significant demethylation in SHG44 instead of A172. However, 5-AZA-CdR treatment had no effect on MAGED4 protein in both SHG44 and A172 cells. In conclusion, MAGED4 is frequently and highly expressed in glioma and is partly regulated by DNA methylation. The results suggest that MAGED4 might be a promising target for glioma immunotherapy combined with 5-AZA-CdR to enhance its expression and eliminate intratumor heterogeneity.
authors.affiliation: Department of Histology and Embryology, School of Pre-clinical Medicine, Guangxi Medical University, Guangxi, China E-mail : xiaoxunxie@gmail.com.
authors.forename: Qing-Mei
authors.initials: QM
authors.lastname: Zhang
authors.forename: Ning
authors.initials: N
authors.lastname: Shen
authors.forename: Sha
authors.initials: S
authors.lastname: Xie
authors.forename: Shui-Qing
authors.initials: SQ
authors.lastname: Bi
authors.forename: Bin
authors.initials: B
authors.lastname: Luo
authors.forename: Yong-Da
authors.initials: YD
authors.lastname: Lin
authors.forename: Jun
authors.initials: J
authors.lastname: Fu
authors.forename: Su-Fang
authors.initials: SF
authors.lastname: Zhou
authors.forename: Guo-Rong
authors.initials: GR
authors.lastname: Luo
authors.forename: Xiao-Xun
authors.initials: XX
authors.lastname: Xie
authors.forename: Shao-Wen
authors.initials: SW
authors.lastname: Xiao
mesh_terms: D000951:Antigens, Neoplasm / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics*; D000077209:Decitabine; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005910:Glioma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000951:Antigens, Neoplasm; D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; C430404:MAGE-E1 antigen, human; D012333:RNA, Messenger; D000077209:Decitabine; D001374:Azacitidine