BRD4 interacts with PML/RAR in acute promyelocytic leukemia

被引：1

作者：

Luo, Qun ^{[1
]}

Deng, Wanglong ^{[1
]}

Wang, Haiwei ^{[2
,3
]}

Fan, Huiyong ^{[1
]}

Zhang, Ji ^{[1
,2
,3
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, State Key Lab Med Genom, Shanghai 200025, Peoples R China

[2] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Shanghai 200025, Peoples R China

[3] Chinese Acad Sci, Grad Sch, Shanghai 200025, Peoples R China

来源：

FRONTIERS OF MEDICINE | 2018年 / 12卷 / 06期

基金：

中国国家自然科学基金;

关键词：

BRD4; PML; RAR; APL; interaction; P-TEFB; SELECTIVE-INHIBITION; CANCER; RECRUITMENT; EPIGENETICS; ELONGATION; MECHANISM; SCREEN;

D O I：

10.1007/s11684-017-0604-x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 (PML/RAR) 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/RAR in NB4 cells. Moreover, downregulation of PML/RAR 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/RAR co-existed on the same regulatory regions of their target genes. Hence, we showed a new discovery of the interaction of BRD4 and PML/RAR, as well as the decline of PML/RAR expression, under JQ1 treatment.

引用

页码：726 / 734

页数：9