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

FASEB J. 2024 Sep 30;38(18):e70058. doi: 10.1096/fj.202400938R.

Abstract

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.

Keywords: UA; aryl hydrocarbon receptor; breast cancer; cell cycle; cyclic protein; reactive oxygen species.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation*
  • Cyclin E* / genetics
  • Cyclin E* / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27* / genetics
  • Cyclin-Dependent Kinase Inhibitor p27* / metabolism
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Nude
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Reactive Oxygen Species / metabolism
  • Receptors, Aryl Hydrocarbon* / genetics
  • Receptors, Aryl Hydrocarbon* / metabolism
  • Signal Transduction
  • Uric Acid* / metabolism

Substances

  • AHR protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • CCNE1 protein, human
  • CDKN1B protein, human
  • Cyclin E
  • Cyclin-Dependent Kinase Inhibitor p27
  • Oncogene Proteins
  • Reactive Oxygen Species
  • Receptors, Aryl Hydrocarbon
  • Uric Acid