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

IF 5.3 2区医学 Q1 ONCOLOGY Cancer Cell International Pub Date : 2024-08-12 DOI:10.1186/s12935-024-03433-y

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

{"title":"Adipocytes promote metastasis of breast cancer by attenuating the FOXO1 effects and regulating copper homeostasis","authors":"Xiu Chen, Heda Zhang, Zheng Fang, Dandan Wang, Yuxin Song, Qian Zhang, Junchen Hou, Sujin Yang, Di Xu, Yinjiao Fei, Wei Zhang, Jian Zhang, Jinhai Tang, Lei Li","doi":"10.1186/s12935-024-03433-y","DOIUrl":null,"url":null,"abstract":"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. 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. 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. Adipocytes might accelerate the progression of breast cancer by modulating FOXO1/miR-135b/ circCNIH4 /EMT axis and regulating copper homeostasis.","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12935-024-03433-y","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

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

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

脂肪细胞通过减弱 FOXO1 作用和调节铜平衡促进乳腺癌转移

肥胖和叉头框O1（FOXO1）会影响乳腺癌患者的生存，但其潜在机制仍不清楚。我们旨在研究FOXO1在肥胖相关性乳腺癌中的作用。我们对南京医科大学第一附属医院2020年收治的383名乳腺疾病患者进行了筛查。我们通过伤口愈合、transwell和matrigel实验来评估癌细胞的转移能力。采用mRNA测序筛选乳腺癌中差异表达的转录本。我们采用免疫组化、Western 印迹和组织芯片来评估 FOXO1 和上皮-间质转化（EMT）通路的水平。我们进行了生物信息学分析，以研究 FOXO1 和 miR-135b 之间的相互作用。我们使用荧光原位杂交、RT-qPCR来确认circCNIH4的特征。我们进行了荧光素酶报告实验和拯救实验来研究 circCNIH4 和 miR-135b 之间的相互作用。肥胖与乳腺癌的发病和进展呈正相关。脂肪细胞增强了乳腺癌的迁移并减弱了FOXO1的作用。MiR-135b 是 FOXO1 的结合基因，并受 circCNIH4 的调控。CircCNIH4在体外和体内都具有抗肿瘤活性。脂肪细胞可能通过调节FOXO1/miR-135b/ circCNIH4/EMT轴和铜平衡加速乳腺癌的进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.