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

Abstract

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.

• Authors: Hanchu Xiong, Zihan Chen, Baihua Lin, Bojian Xie, Xiaozhen Liu, Cong Chen, Zhaoqing Li, Yunlu Jia, Zhuazhua Wu, Min Yang, Yongshi Jia, Linbo Wang, Jichun Zhou, Xuli Meng
• Journal: Frontiers in immunology (Front Immunol) Vol. 12 Pg. 745111 ( 2021) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 35087512 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Xiong, Chen, Lin, Xie, Liu, Chen, Li, Jia, Wu, Yang, Jia, Wang, Zhou and Meng.

Chemical References

• Flavanones
• NF-E2-Related Factor 2
• NFE2L2 protein, human
• NR3C1 protein, human
• Receptors, Glucocorticoid
• Tacrolimus Binding Proteins
• tacrolimus binding protein 4
• naringenin

Topics

• Animals
• Autophagy (drug effects)
• Breast Neoplasms (drug therapy, metabolism)
• Cell Differentiation (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dendritic Cells (drug effects, metabolism)
• Female
• Flavanones (pharmacology)
• Gene Expression Regulation (drug effects)
• Humans
• MCF-7 Cells
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• NF-E2-Related Factor 2 (metabolism)
• Receptors, Glucocorticoid (metabolism)
• Signal Transduction (drug effects)
• Tacrolimus Binding Proteins (metabolism)
• Tumor Microenvironment (drug effects)