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<p>Epigenetic modifications, particularly DNA methylation, play a critical role in the metastatic progression of breast cancer. This study investigates the role of DNA methyltransferase 1 (DNMT1) in regulating the methylation of RASSF1A and its contribution to breast cancer brain metastasis. Using single-cell transcriptome sequencing of CTCs derived from in situ breast cancer models, DNMT1 was identified as a key promoter of tumor cell viability, migration, and invasion. RASSF1A was further validated as a direct target of DNMT1-mediated methylation. This regulatory interaction was confirmed through DNA methylation sequencing, methylation-specific PCR, and chromatin immunoprecipitation assays. These findings highlight the pivotal role of DNMT1-driven RASSF1A methylation in facilitating breast cancer metastasis to the brain, and suggest that targeting DNMT1 may represent a promising therapeutic approach for managing metastatic breast cancer.</p>

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DNMT1 modulation of RASSF1A methylation enhances breast cancer brain metastasis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月11日

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  • Qianqian Cao,
  • Gongwen Xu,
  • Guanghui Huang,
  • Sheng Li,
  • Hao Li,
  • Xiaonan Zhang,
  • Xiaomei Li

摘要

Epigenetic modifications, particularly DNA methylation, play a critical role in the metastatic progression of breast cancer. This study investigates the role of DNA methyltransferase 1 (DNMT1) in regulating the methylation of RASSF1A and its contribution to breast cancer brain metastasis. Using single-cell transcriptome sequencing of CTCs derived from in situ breast cancer models, DNMT1 was identified as a key promoter of tumor cell viability, migration, and invasion. RASSF1A was further validated as a direct target of DNMT1-mediated methylation. This regulatory interaction was confirmed through DNA methylation sequencing, methylation-specific PCR, and chromatin immunoprecipitation assays. These findings highlight the pivotal role of DNMT1-driven RASSF1A methylation in facilitating breast cancer metastasis to the brain, and suggest that targeting DNMT1 may represent a promising therapeutic approach for managing metastatic breast cancer.