• UHRF1 is upregulated in breast cancer tissues and cell lines, and its knockdown suppresses proliferation and invasion while inducing cell cycle arrest and apoptosis.
• UHRF1 epigenetically silences ZBTB16 via DNMT1-mediated promoter methylation, revealing a novel regulatory axis.
• The ZBTB16/ANXA7/Cyclin B1 axis mediates the tumor-suppressive effects of UHRF1 knockdown, providing potential therapeutic targets.
• In vivo xenograft studies confirm that UHRF1 knockdown reduces tumor growth, supporting its clinical relevance.