Increasing RB1 Expression by Targeting EZH2 in Triple-Negative Breast Cancer.

ABSTRACT: Loss of RB1 function represents a defining characteristic of triple-negative breast cancer (TNBC) and is intricately associated with resistance to therapeutic interventions. In this study, we investigate the epigenetic mechanisms governing RB1 expression in TNBC. Employing a combination of bioinformatics analyses and experimental validations, we identified lysine histone methyltransferase EZH2 as a key upstream regulator of RB1 expression. EZH2 primarily mediates trimethylation of lysine 27 on histone H3 as the catalytic subunit of the Polycomb repressive complex 2 (PRC2) complex. Furthermore, our findings demonstrate that pharmacological inhibition of EZH2 leads to a significant upregulation of RB1 expression levels, mediated by enhanced enrichment of the activating histone marker H3K27ac

SUBMITTER: Yang R 

PROVIDER: S-EPMC11897054 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature