Dysregulated DNA methylation in cancer is critical in the transcription machinery associated with cancer progression. Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, but no treatment targeting TNBC biomarkers has yet been developed. To identify specific DNA methylation patterns in TNBC, methyl-binding domain protein 2 (MBD) sequencing data were compared in TNBC and the three other major breast cancer subtypes. Integrated analysis of DNA methylation and gene expression identified a gene set showing a correlation between DNA methylation and gene expression. ATPase Na+/K+-transporting subunit alpha 1 (ATP1A1) was found to be specifically hypomethylated in the coding sequence (CDS) region and to show increased expression in TNBC. The Cancer Genome Atlas (TCGA) database also showed that hypomethylation and high expression of ATP1A1 were strongly associated with poor survival in patients with TNBC. Furthermore, ATP1A1 knockdown significantly reduced the viability and tumor-sphere formation of TNBC cells. These results suggest that the hypomethylation and overexpression of ATP1A1 could be a prognostic marker in TNBC and that the manipulation of ATP1A1 expression could be a therapeutic target in this disease.
癌症中DNA甲基化的失调在与癌症进展相关的转录机制中至关重要。三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌亚型，但尚未开发出针对TNBC生物标志物的治疗方法。为了识别TNBC中特定的DNA甲基化模式，我们比较了TNBC与其他三种主要乳腺癌亚型中甲基结合域蛋白2（MBD）测序数据。通过整合分析DNA甲基化与基因表达，鉴定出一组显示DNA甲基化与基因表达相关性的基因。研究发现，ATP酶Na+/K+转运亚基α1（ATP1A1）在编码序列（CDS）区域特异性低甲基化，并在TNBC中表达增加。癌症基因组图谱（TCGA）数据库也显示，ATP1A1的低甲基化和高表达与TNBC患者的不良生存率密切相关。此外，敲低ATP1A1显著降低了TNBC细胞的活性和肿瘤球形成能力。这些结果表明，ATP1A1的低甲基化和过表达可能是TNBC的预后标志物，而调控ATP1A1的表达可能成为该疾病的治疗靶点。
肿瘤(癌症)患者之家