biostudies-literatureUnknown17(1)Cao QEpigenetic 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 Cell death & disease80https://www.ebi.ac.uk/biostudies/studies/S-EPMC12830775biostudies-literatureDNMT1 modulation of RASSF1A methylation enhances breast cancer brain metastasis.PMC12830775Li HLi XLi SHuang GZhang XXu GCao QfalseDNMT1 modulation of RASSF1A methylation enhances breast cancer brain metastasis.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 2025-01-01T00:00:00Z2025 Dec2026-06-06T20:13:32.421Z2026-06-04T03:14:00.505ZS-EPMC128307754138144010.1038/s41419-025-08167-x