MAGI2-AS3 inhibits breast cancer by downregulating DNA methylation of MAGI2

MAGI2-AS3 inhibits breast cancer by downregulating DNA methylation of MAGI2
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MAGI2-AS3 通过下调 MAGI2 DNA 甲基化抑制乳腺癌

DOI:
10.1002/jcp.29922
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发表时间:
2020-07-30
影响因子:
5.6
通讯作者:
Zhang, Jingwei
Zhang, Jingwei
中科院分区:
生物学2区
文献类型:
--
作者:
Xu, Xiaolong;Yuan, Xiaoning;Zhang, Jingwei

文献摘要

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乳腺癌是对妇女最具威胁的疾病之一。据报道,长链非编码rna参与了乳腺癌的发展。在本研究中,我们分析了The Cancer Genome Atlas乳腺癌组织高通量测序数据,筛选并验证了低表达的长链非编码RNA MAGI2-AS3。通过基因共表达分析,我们发现MAGI2- as3与MAGI2具有良好的表达相关性。在乳腺癌细胞MCF-7中过表达MAGI2- as3或MAGI2会抑制Wnt/ β -catenin通路,抑制细胞增殖和迁移。基因结构和DNA甲基化分析结果表明,MAGI2- as3可能作为顺式调控元件下调MAGI2启动子区DNA甲基化水平,DNA去甲基化酶TET1抑制剂可逆转MAGI2- as3过表达导致的MAGI2上调和细胞效应。我们的研究结果揭示了MAGI2-AS3在乳腺癌中的作用,并为转移性乳腺癌干预提供了潜在的新治疗靶点。
Breast cancer is one of the most threatening diseases for women. Long noncoding RNAs were reported to be involved in breast cancer development. In this study, we analyzed The Cancer Genome Atlas breast cancer tissue high-throughput sequencing data and screened and validated the low-expressing long noncoding RNA named MAGI2-AS3. Through gene coexpression analysis, we found that MAGI2-AS3 has a good expression correlation with MAGI2. Overexpression of MAGI2-AS3 or MAGI2 in breast cancer cells MCF-7 would inhibit the Wnt/beta-catenin pathway and inhibit cell proliferation and migration. Gene structure and DNA methylation analysis results indicated that MAGI2-AS3 may act as a cis-acting regulatory element downregulating the DNA methylation level of the MAGI2 promoter region, and the DNA demethylase TET1 inhibitor can reverse MAGI2-AS3 overexpression caused upregulation of MAGI2 and cellular effects. Our findings reveal the role of MAGI2-AS3 in breast cancer and provide potential novel therapeutic targets for metastatic breast cancer intervention.