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尿囊素通过 AhR/p27/cyclin E 通路影响乳腺癌的进展。

UA influences the progression of breast cancer via the AhR/p27/cyclin E pathway.

机构信息

Laboratory of Vascular Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.

Department of Breast Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.

出版信息

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/p27/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/p27/cyclin E1 pathway axis.

摘要

尿酸(UA)是嘌呤代谢的终产物。近年来,UA 被发现与临床癌症患者的预后相关。然而,UA 影响肿瘤患者发生和预后的复杂机制尚未得到充分阐明。在这项研究中,我们探讨了 UA 在乳腺癌中的作用,通过用 UA 处理两种类型的乳腺癌细胞系来研究其对乳腺癌细胞功能的影响。进一步研究了 UA 在肿瘤细胞周期和增殖中的作用及其潜在机制。我们发现 UA 的抗氧化作用促进了乳腺癌中活性氧(ROS)的清除,从而降低了芳香烃受体(AhR)的表达并影响乳腺癌细胞周期,通过 AhR/p27/cyclin E1 通路驱动乳腺癌细胞增殖。此外,在乳腺癌患者中,AhR 及其下游基因的表达可能与患者的癌症进展密切相关。因此,UA 的增加可能通过 AhR/p27/cyclin E1 通路轴促进乳腺癌细胞的增殖。

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