Hypomethylation of ATP1A1 Is Associated with Poor Prognosis and Cancer Progression in Triple-Negative Breast Cancer

Yesol Kim, Je Yeong Ko, Hyun Kyung Kong, Minyoung Lee, Woosung Chung, Sera Lim, Dasom Son, Sumin Oh, Jee Won Park, Do Yeon Kim, Minju Lee, Wonshik Han, Woong Yang Park, Kyung Hyun Yoo, Jong Hoon Park

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number1666
JournalCancers
Volume16
Issue number9
DOIs
StatePublished - May 2024

Keywords

  • ATP1A1
  • DNA methylation
  • prognostic marker
  • triple-negative breast cancer

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