Methyltransferase 3A-mediated promoter methylation represses retinoic acid receptor responder 3 expression in basal-like breast cancer
作者机构：Department of Pancreatic SurgeryWest China HospitalSichuan UniversityChengdu610041China
出 版 物：《BIOCELL》 (生物细胞（英文）)
年 卷 期：2023年第47卷第2期
页 面：319-328页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：supported by the Science&Technology Department of Sichuan Province China(2022YFS0314)
主 题：DNMT3A Basal-like breast cancer RARRES3 Promoter methylation
摘 要：Retinoic acid receptor responder 3(RARRES3)has been characterized as a tumor suppressor in multiple types of *** study aimed to examine the expression profile of RARRES3 across the PAM50 subtypes of breast *** DNA methylation status of RARRES3 was checked in the basal-like subtype,and the underlying mechanisms of its dysregulation were ***-sequencing(seq)and methylation data from The Cancer Genome Atlas were used for in-silico ***-like representative SUM149 and MDA-MB-468 cell lines were used for in vitro and in vivo *** to tumor-adjacent normal tissues,only the basal-like tumor tissues had significantly downregulated RARRES3 *** methylation level of four CpG sites in the promoter region showed a strong negative correlation with RARRES3 *** gene coding for DNA methyltransferase 3A(DNMT3A)had consistent positive correlations with the methylation of the CpG *** Immunoprecipitation-quantitative polymerase chain-reaction and bisulfite sequencing PCR showed that DNMT3A could bind to the promoter region of RARRES3 and promote methylation of the CpG sites within the ***3A knockdown significantly restored RARRES3 expression at the mRNA and protein level in the two cell ***-8,colony formation,and flow cytometric analysis showed that RARRES3 overexpression attenuated the growth-promoting effects of DNMT3A overexpression and also weakened the DNMT3A overexpression-induced activation of ERK1/2 and PI3K/AKT *** summary,this study revealed that DNMT3A enhances promoter methylation of the RARRES3 gene and suppresses its transcription in basal-like breast *** DNMT3A-RARRES3 signaling pathway might be a potential target for the treatment of this tumor subtype.
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