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Series GSE77568 Query DataSets for GSE77568
Status Public on Feb 05, 2017
Title Inhibition of BET protein BRD4 activity synergizes with cisplatin in ovarian cancer by targeting ALDH activity through an ALDH1A1 super-enhancer and the associated enhancer RNA
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary The emergence of tumor cells with certain stem-like characteristics such as high aldehyde dehydrogenase (ALDH) activity contributes to chemotherapy resistance. Here we report that inhibition of the BET protein BRD4 potentiates the tumor suppressive effects of cisplatin by targeting ALDH activity. The clinically applicable small molecule BET inhibitor JQ1 synergized with cisplatin by suppressing the growth of epithelial ovarian cancer cells both in vitro and in vivo. This correlated with the suppression of ALDH activity and ALDH1A1 gene expression. BRD4 regulates ALDH1A1 gene transcription through a super-enhancer and expression of its associated enhancer RNA. Thus, targeting the BET protein BRD4 using clinical applicable small molecule inhibitors such as JQ1 is a promising strategy to enhance cisplatin response.
Overall design DMSO and JQ1 treated cells were assayed by BRD4 CHIP-seq and RNA-seq
Contributor(s) Yokoyama Y, Zhang R
Citation(s) 27803105, 29262321
Submission date Feb 04, 2016
Last update date Jun 13, 2019
Contact name Priyankara J Wickramasinghe
Phone 2154956837
Organization name The Wistar Institute
Department Bioinformatics
Lab Genomics
Street address 3601 Spruce Street
City Philadelphia
State/province PA
ZIP/Postal code 19104
Country USA
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (5)
GSM2054575 BRD4 CHIP-seq in DMSO-treated cells
GSM2054576 BRD4 CHIP-seq in JQ1-treated cells
GSM2054577 input control
BioProject PRJNA310832
SRA SRP069290

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Supplementary file Size Download File type/resource
GSE77568_CHIP_DMSO_vs_JQ1.txt.gz 384.5 Kb (ftp)(http) TXT
GSE77568_CHIP_DMSO_vs_input.txt.gz 522.3 Kb (ftp)(http) TXT
GSE77568_RNA_DMSO_JQ1_expression.txt.gz 1009.8 Kb (ftp)(http) TXT
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