BRD4 interacts with PML/RARα in acute promyelocytic leukemia.
10.1007/s11684-017-0604-x
- Author:
Qun LUO
1
;
Wanglong DENG
1
;
Haiwei WANG
2
;
Huiyong FAN
1
;
Ji ZHANG
3
Author Information
1. State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
2. Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Graduate School, Chinese Academy of Sciences, Shanghai, 200025, China.
3. State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. jizhang@sibs.ac.cn.
- Publication Type:Journal Article
- Keywords:
APL;
BRD4;
PML/RARα;
interaction
- MeSH:
Apoptosis;
drug effects;
Azepines;
pharmacology;
Cell Differentiation;
Down-Regulation;
Gene Expression Regulation, Neoplastic;
drug effects;
Humans;
Leukemia, Promyelocytic, Acute;
drug therapy;
genetics;
Nuclear Proteins;
genetics;
Promyelocytic Leukemia Protein;
genetics;
RNA, Messenger;
genetics;
Retinoic Acid Receptor alpha;
genetics;
Transcription Factors;
genetics;
Triazoles;
pharmacology;
Tumor Cells, Cultured
- From:
Frontiers of Medicine
2018;12(6):726-734
- CountryChina
- Language:English
-
Abstract:
Bromodomain-containing 4 (BRD4) has been considered as an important requirement for disease maintenance and an attractive therapeutic target for cancer therapy. This protein can be targeted by JQ1, a selective small-molecule inhibitor. However, few studies have investigated whether BRD4 influenced acute promyelocytic leukemia (APL), and whether BRD4 had interaction with promyelocytic leukemia-retinoic acid receptor α (PML/RARα) fusion protein to some extent. Results from cell viability assay, cell cycle analysis, and Annexin-V/PI analysis indicated that JQ1 inhibited the growth of NB4 cells, an APL-derived cell line, and induced NB4 cell cycle arrest at G1 and apoptosis. Then, we used co-immunoprecipitation (co-IP) assay and immunoblot to demonstrate the endogenous interaction of BRD4 and PML/RARα in NB4 cells. Moreover, downregulation of PML/RARα at the mRNA and protein levels was observed upon JQ1 treatment. Furthermore, results from the RT-qPCR, ChIP-qPCR, and re-ChIP-qPCR assays showed that BRD4 and PML/RARα co-existed on the same regulatory regions of their target genes. Hence, we showed a new discovery of the interaction of BRD4 and PML/RARα, as well as the decline of PML/RARα expression, under JQ1 treatment.
