General mechanism of JQ1 in inhibiting various types of cancer

doi:10.3892/mmr.2020.10927

科研成果详情

题名	General mechanism of JQ1 in inhibiting various types of cancer
作者	Jiang, Guojuan 1; Deng, Wanglong 1; Liu, Yang 1; Wang, Chengde2
发表日期	2020-03
发表期刊	MOLECULAR MEDICINE REPORTS 影响因子和分区
语种	英语
原始文献类型	Article
关键词	small molecular compound bromodomain-containing 4 inhibitor JQ1
其他关键词	BROMODOMAIN PROTEIN BRD4 ; TRANSCRIPTIONAL ELONGATION ; CELL IDENTITY ; P-TEFB ; SELECTIVE-INHIBITION ; SUPER-ENHANCERS ; PAUSE RELEASE ; BET ; RECRUITMENT ; INFLAMMATION
摘要	Bromodomain-containing 4 (BRD4) is a histone modification reader and transcriptional regulator that has been reported to interact with acetylated lysine histone motifs transcription factors (TFs), transcription co-activators and RNA polymerase II. The selective small molecule inhibitor JQ1, which binds competitively to bromodomains, has been reported to exhibit anti-proliferative effects in various types of cancer. Previous studies on the mechanism of action of JQ1 mostly focused on a specific tumor type or disease; however, the general mechanism through which JQ1 affects various tumors remains to be determined. In the present study, chromatin immunoprecipitation sequencing data for BRD4 and its expression profiles in six cancer cell lines were integrated and analyzed systematically. The results indicated that BRD4 binds to enhancers with histone H3 acetylated at lysine 27 (H3K27Ac) and mediator complex subunit 1 in a cell type-specific manner, as well as binds to promoter regions with the oncogenic TFs MYC and E2F1 in a cell type-common manner. The cell type-common sites across the six cell types investigated were found to be functionally important for tumorigenesis, whereas the cell type-specific sites were functionally enriched with the cell identity, all of which were sensitive to JQ1 treatment. Furthermore, a core set of JQ1-regulated BRD4 binding genes were obtained, which were significantly inhibited by JQ1 in various cancer cell lines and contributed to hallmarks of cancer. These results implied a common mechanism underlying the therapeutic effects of JQ1 and suggested its potential suitability as an anti-cancer drug targeting BRD4-mediated transcriptional regulation.
资助项目	Zhejiang Provincial Department of Health Project [2018KY515]; Key Research Project of Traditional Chinese Medicine of Zhejiang Province of China [2019ZZ015]
出版者	SPANDIDOS PUBL LTD
出版地	ATHENS
ISSN	1791-2997
EISSN	1791-3004
卷号	21 期号:3 页码:1021-1034
DOI	10.3892/mmr.2020.10927
页数	14
WOS类目	Oncology ; Medicine, Research & Experimental
WOS研究方向	Oncology ; Research & Experimental Medicine
WOS记录号	WOS:000515676300005
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
Pubmed记录号	31922235
PMC记录号	PMC7003028
Scopus记录号	2-s2.0-85078734568
通讯作者地址	[Jiang, Guojuan]State Key Laboratory of Medical Genomics,Shanghai Institute of Hematology,Rui Jin Hospital Affiliated to School of Medicine,Shanghai Jiao Tong University,227 Chongqing South Road,Shanghai,200025,China
scopus学科分类	Biochemistry;Molecular Medicine;Molecular Biology;Genetics;Oncology;Cancer Research
引用统计	被引频次：15[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/4651
专题	附属第一医院_神经外科
通讯作者	Jiang, Guojuan
作者单位	1.State Key Laboratory of Medical Genomics,Shanghai Institute of Hematology,Rui Jin Hospital Affiliated to School of Medicine,Shanghai Jiao Tong University,Shanghai,200025,China; 2.Department of Neurosurgery,First Affiliated Hospital of Wenzhou Medical University,2 Fu Xue Lane,Wenzhou, Zhejiang,325000,China
推荐引用方式 GB/T 7714	Jiang, Guojuan,Deng, Wanglong,Liu, Yang,et al. General mechanism of JQ1 in inhibiting various types of cancer[J]. MOLECULAR MEDICINE REPORTS,2020,21(3):1021-1034.
APA	Jiang, Guojuan, Deng, Wanglong, Liu, Yang, & Wang, Chengde. (2020). General mechanism of JQ1 in inhibiting various types of cancer. MOLECULAR MEDICINE REPORTS, 21(3), 1021-1034.
MLA	Jiang, Guojuan,et al."General mechanism of JQ1 in inhibiting various types of cancer".MOLECULAR MEDICINE REPORTS 21.3(2020):1021-1034.