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

IF 4.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY FASEB Journal Pub Date : 2024-09-25 DOI:10.1096/fj.202400938R

Zhiying Wang, Yuanqi Zhang, Shengchao Huang, Zhihong Liao, Mingzhang Huang, Wei Lei, Xiaorong Shui

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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^Kip1/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^Kip1/cyclin E1 pathway axis.

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UA 通过 AhR/p27Kip1/cyclin E 通路影响乳腺癌的进展

尿酸（UA）是嘌呤代谢的最终产物。近年来，人们发现尿酸与临床癌症患者的预后有关。然而，尿酸影响肿瘤患者病情发展和预后的复杂机制尚未得到很好的阐明。在这项研究中，我们探讨了 UA 在乳腺癌中的作用，通过用 UA 处理两种乳腺癌细胞系，仔细研究其对乳腺癌细胞功能的影响。我们还进一步研究了 UA 在肿瘤细胞周期和增殖中的作用及其内在机制。我们发现，UA的抗氧化作用有利于清除乳腺癌细胞中的活性氧（ROS），从而降低芳香烃受体（AhR）的表达，影响乳腺癌细胞周期，通过AhR/p27Kip1/细胞周期蛋白E1途径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 的增加可通过 AhR/p27Kip1/cyclin E1 通路轴促进乳腺癌细胞的增殖。

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来源期刊

FASEB Journal 生物-生化与分子生物学

CiteScore

9.20

自引率

2.10%

发文量

6243

审稿时长

3 months

期刊介绍： The FASEB Journal publishes international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research. In addition to research, review, and hypothesis submissions, The FASEB Journal also seeks perspectives, commentaries, book reviews, and similar content related to the life sciences in its Up Front section.