Naringenin Regulates FKBP4/NR3C1/NRF2 Axis in Autophagy and Proliferation of Breast Cancer and Differentiation and Maturation of Dendritic Cell

Frontiers in Immunology

Xiaozhen Liu¹  Xuli Meng¹  Min Yang²  Hanchu Xiong²  Zhuazhua Wu²  Yongshi Jia²  Baihua Lin²  Bojian Xie³  Yunlu Jia⁴  Jichun Zhou⁵  Cong Chen⁵  Zhaoqing Li⁵  Linbo Wang⁵  Zihan Chen⁶ 

[1] Cancer Center, Department of Breast Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, China;Cancer Center, Department of Radiation Oncology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China;Department of Breast and Thyroid Surgery, Taizhou Hospital of Zhejiang Province, Taizhou, China;Department of Medical Oncology, First Affiliated Hospital, Zhejiang University, Hangzhou, China;Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China;Surgical Intensive Care Unit, First Affiliated Hospital, Zhejiang University, Hangzhou, China;

关键词: FKBP4;    NRF2;    NR3C1;    autophagy;    Dendritic cell;    Breast cancer;   

DOI  :  10.3389/fimmu.2021.745111

来源: DOAJ

【 摘 要 】

NRF2 is an important regulatory transcription factor involved in tumor immunity and tumorigenesis. In this study, we firstly identified that FKBP4/NR3C1 axis was a novel negative regulator of NRF2 in human breast cancer (BC) cells. The effect of FKBP4 appeared to be at protein level of NRF2 since it could not suppress the expression of NRF2 at mRNA level. Bioinformatics analysis and in vitro experiments further demonstrated that FKBP4 regulated NRF2 via regulating nuclear translocation of NR3C1. We then reported that naringenin, a flavonoid, widely distributed in citrus and tomato, could suppress autophagy and proliferation of BC cells through FKBP4/NR3C1/NRF2 signaling pathway in vitro and in vivo. Naringenin was also found to promote dendritic cell (DC) differentiation and maturation through FKBP4/NR3C1/NRF2 axis. Therefore, our study found that naringenin could induce inhibition of autophagy and cell proliferation in BC cells and enhance DC differentiation and maturation, at least in part, though regulation of FKBP4/NR3C1/NRF2 signaling pathway. Identification of FKBP4/NR3C1/NRF2 axis would provide insights for novel anti-tumor strategy against BC among tumor microenvironment.

【 授权许可】

Unknown