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MAGI2-AS3 通过下调 MAGI2 的 DNA 甲基化抑制乳腺癌。

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

机构信息

Department of Pathology and Pathophysiology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China.

Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

J Cell Physiol. 2021 Feb;236(2):1116-1130. doi: 10.1002/jcp.29922. Epub 2020 Jul 30.

Abstract

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/β-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.

摘要

乳腺癌是女性最具威胁性的疾病之一。长链非编码 RNA 被报道参与乳腺癌的发生。在这项研究中,我们分析了癌症基因组图谱乳腺癌组织高通量测序数据,并筛选和验证了低表达的长链非编码 RNA,命名为 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 通路并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 可能作为顺式作用调节元件,下调 MAGI2 启动子区域的 DNA 甲基化水平,而 DNA 去甲基化酶 TET1 抑制剂可以逆转 MAGI2-AS3 过表达引起的 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。

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