脂肪细胞通过减弱FOXO1的作用和调节铜稳态来促进乳腺癌转移。

Adipocytes promote metastasis of breast cancer by attenuating the FOXO1 effects and regulating copper homeostasis.

作者信息

Chen Xiu, Zhang Heda, Fang Zheng, Wang Dandan, Song Yuxin, Zhang Qian, Hou Junchen, Yang Sujin, Xu Di, Fei Yinjiao, Zhang Wei, Zhang Jian, Tang Jinhai, Li Lei

机构信息

Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, Jiangsu, China.

Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China.

出版信息

Cancer Cell Int. 2024 Aug 12;24(1):284. doi: 10.1186/s12935-024-03433-y.

DOI:10.1186/s12935-024-03433-y

PMID:39135158

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11320833/

Abstract

BACKGROUND

Obesity and the forkhead box O1(FOXO1) affect the survival of breast cancer patients, but the underlying mechanism remains unclear. We aimed to investigate the role of FOXO1 in obesity-associated-breast cancer.

METHODS

We screened 383 breast disease patients from the first affiliated hospital with Nanjing Medical University in 2020. We performed wound healing, transwell, matrigel assays to assess the metastatic ability of cancer cells. We adopted mRNAs sequencing to select the differentially expressed transcripts in breast cancer. We applied immunohistochemistry, western blot, tissue microarrays to assess the level of FOXO1 and epithelial-mesenchymal transition (EMT) pathways. We conducted bioinformatic analysis to investigate interactions between FOXO1 and miR-135b. We used fluorescence in situ hybridization, RT-qPCR to confirm the characteristics of circCNIH4. We conducted luciferase reporter assay, rescue experiments to investigate interactions between circCNIH4 and miR-135b.

RESULTS

Obesity was positively correlated with the incidence and progression of breast cancer. Adipocytes enhanced the migration of breast cancer and attenuated the effects of FOXO1. MiR-135b was a binding gene of FOXO1 and was regulated by circCNIH4. CircCNIH4 exhibited antitumor activity in vitro and in vivo.

CONCLUSION

Adipocytes might accelerate the progression of breast cancer by modulating FOXO1/miR-135b/ circCNIH4 /EMT axis and regulating copper homeostasis.

摘要

背景

肥胖和叉头框O1（FOXO1）影响乳腺癌患者的生存，但潜在机制仍不清楚。我们旨在研究FOXO1在肥胖相关乳腺癌中的作用。

方法

2020年，我们从南京医科大学第一附属医院筛选了383例乳腺疾病患者。我们进行了伤口愈合、Transwell、基质胶实验以评估癌细胞的转移能力。我们采用mRNA测序来选择乳腺癌中差异表达的转录本。我们应用免疫组织化学、蛋白质免疫印迹法、组织芯片来评估FOXO1和上皮-间质转化（EMT）通路的水平。我们进行生物信息学分析以研究FOXO1与miR-135b之间的相互作用。我们使用荧光原位杂交、逆转录定量聚合酶链反应来确认环状神经胶质瘤相关同源物4（circCNIH4）的特征。我们进行荧光素酶报告基因实验、挽救实验来研究circCNIH4与miR-135b之间的相互作用。