The p53/ZEB1-PLD3 feedback loop regulates cell proliferation in breast cancer

Breast cancer is the most prevalent cancer globally, endangering women’s physical and mental health. Phospholipase D3 (PLD3) belongs to the phosphodiesterase family (PLD). PLD3 is related to insulin-mediated phosphorylation of the AKT pathway, suggesting that it may play a role in the occurrence and development of malignant tumors. This study may further explore the molecular mechanism of PLD3 inhibiting breast cancer cell proliferation. In this study, we demonstrated that PLD3 and miR-6796 are co-expressed in breast cancer. PLD3 can bind with CDK1 and inhibit its expression, leading to mitotic arrest and inhibiting breast cancer proliferation. Wild-type p53 regulates PLD3 and miR-6796 expression by competitively binding to the PLD3 promoter with ZEB1. DNMT3B, as the target gene of miR-6796, is recruited into the PLD3 promoter by combining with ZEB1 to regulate the DNA methylation of the PLD3 promoter and ultimately affect PLD3 and miR-6796 expression. In conclusion, we revealed the role and molecular mechanism of PLD3 and its embedded miR-6796 in breast cancer proliferation, providing clues and a theoretical foundation for future research and development of therapeutic targets and prognostic markers for breast cancer.