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Series GSE84405 Query DataSets for GSE84405
Status Public on Jul 14, 2017
Title ARID1A-mutated ovarian cancers depend on HDAC6 activity
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary ARID1A, encoding a subunit of the SWI/SNF chromatin remodeling complex, is the most mutated epigenetic regulator in human cancers. ARID1A and TP53 mutations are typically mutually exclusive. Therapeutic approaches that correlate with ARID1A mutational status remain a challenge. Here, we show that HDAC6 activity is essential in ARID1A-mutated ovarian cancers. Inhibition of HDAC6 activity using a clinically applicable small molecule inhibitor significantly improved the survival of mice bearing ARID1A-mutated ovarian tumors. This correlated with the suppression of growth and dissemination of ARID1A-mutated, but not wild-type, tumors. The dependence on HDAC6 activity in ARID1A-mutated cells correlated with a direct transcriptional repression of HDAC6 by ARID1A. HDAC6 inhibition selectively promoted apoptosis of ARID1A-mutated cells. HDAC6 directly deacetylated the Lysine 120 residue of p53, a pro-apoptotic post-translational modification. Thus, ARID1A mutation inactivates p53’ apoptotic function by upregulating HDAC6. These results indicate that pharmacological inhibition of HDAC6 is a novel therapeutic strategy involving ARID1A-mutation
Overall design RNA-seq transcription profiling of samples with altered HDAC6 activity
Contributor(s) Bitler BG, Zhang R
Citation(s) 28737768
Submission date Jul 14, 2016
Last update date May 15, 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 (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (5)
GSM2233129 shControl
GSM2233130 Vehicle control
GSM2233131 shHDAC6
BioProject PRJNA329095
SRA SRP078500

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Supplementary file Size Download File type/resource
GSE84405_Bitler_Zhang_gene_processed.txt.gz 1.2 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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