UA influences the progression of breast cancer via the AhR/p27Kip1/cyclin E pathway

Uric acid (UA) is the end product of purine metabolism. In recent years, UA has been found to be associated with the prognosis of clinical cancer patients. However, the intricate mechanisms by which UA affects the development and prognosis of tumor patients has not been well elucidated. In this study, we explored the role of UA in breast cancer, scrutinizing its impact on breast cancer cell function by treating two types of breast cancer cell lines with UA. The role of UA in the cell cycle and proliferation of tumors and the underlying mechanisms were further investigated. We found that the antioxidant effect of UA facilitated the scavenging of reactive oxygen species (ROS) in breast cancer, thereby reducing aryl hydrocarbon receptor (AhR) expression and affecting the breast cancer cell cycle, driving the proliferation of breast cancer cells through the AhR/p27Kip1/cyclin E1 pathway. Moreover, in breast cancer patients, the expression of AhR and its downstream genes may be closely associated with cancer progression in patients. Therefore, an increase in UA could promote the proliferation of breast cancer cells through the AhR/p27Kip1/cyclin E1 pathway axis. Uric acid (UA) has been found to be associated with the prognosis of clinical cancer patients. We investigated the mechanisms underlying the crosstalk between UA and breast cancer progression. Our findings revealed that UA facilitated the scavenging of reactive oxygen species (ROS) in breast cancer, thereby reducing AhR expression and influencing the breast cell cycle, ultimately driving the proliferation of breast cancer cells. Cyclin-dependent kinase inhibitor (p27Kip1), a cell cycle inhibitor and direct transcriptional target of AhR, may be down-regulated by AhR, further promoting the expression of cyclin E1. This, in turn, facilitates the proliferation of breast cancer cells by triggering more of them to enter the proliferative active cell cycle. Therefore, an increase in UA levels could promote the proliferation of breast cancer cells through the AhR/p27Kip1/cyclin E1 pathway axis. These findings suggest that elevated UA levels might exacerbate breast cancer progression by modulating cell cycle homeostasis.image