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.

中文翻译：

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MAGI2-AS3 通过下调 MAGI2 的 DNA 甲基化来抑制乳腺癌。

乳腺癌是对女性威胁最大的疾病之一。据报道，长链非编码 RNA 与乳腺癌的发展有关。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，筛选并验证了名为 MAGI2-AS3 的低表达长链非编码 RNA。通过基因共表达分析，我们发现MAGI2-AS3与MAGI2有很好的表达相关性。MAGI2-AS3或MAGI2在乳腺癌细胞MCF-7中的过表达会抑制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控元件下调MAGI2启动子区域的DNA甲基化水平，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。