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Series GSE55031 Query DataSets for GSE55031
Status Public on Feb 12, 2016
Title Activation of the P-TEFb Complex by Lethal Prostate Cancer-Associated Enhancer RNAs [ChIP-Seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Castration resistant prostate cancer (CRPC) is a lethal disease1-4. Aberrant activation of the androgen receptor (AR) becomes a central mechanism contributing to the resistance of endocrine therapies2,3. Here we demonstrate that non-coding RNAs transcribed from the AR bound-enhancers RNAs (AR-eRNAs) are upregulated in human CRPC cells in vitro, xenografts in vivo and patient tissues. Expression of a subset of genes with elevated AR-eRNAs, including TLE1 and HTR3A, is inversely correlated with biochemical recurrence-free survival of CRPC patients. We identify aan HIV-1 TAR-like (TAR-L) motif in AR-eRNAs of AR target genes including KLK3 (or PSA) and TMPRSS2. The TAR-L motif is important for these eRNAs to bind to CYCLIN T1 of the positive transcription elongation factor b (P-TEFb) complex. Knockdown of PSA eRNA diminishes RNA polymerase II (Pol II) serine-2 (Ser-2) phosphorylation at the PSA promoter. The TAR-L motif in KLK3 eRNA is crucial for effective transcription of PSA mRNA. Together, wWe demonstrate a P-TEFb activation function of eRNA and reveal aberrant eRNA expression as a functional indicator of AR abnormality in CRPC. Our results also suggest that eRNAs as amay be a potential target for CRPC therapy.
Overall design Androgen receptor (AR) binding sites in human prostate cancer cell lines, LNCaP and C4-2, were studied using ChIP-seq. ChIP enriched and input DNA were sequenced using Illumina HiSeq 2000.
Contributor(s) Huang H, Zhao Y, Wang L
Citation(s) 27068475, 27221037
Submission date Feb 14, 2014
Last update date Mar 27, 2020
Contact name LIGUO WANG
Organization name Mayo Clinic
Department Division of Computational Biology
Street address 200 1st St SW
City Rochester
State/province MN
ZIP/Postal code 55905
Country USA
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (6)
GSM1328165 C4-2_EtOH
GSM1328166 C4-2_Mib
GSM1328167 C4-2_input
This SubSeries is part of SuperSeries:
GSE55032 Activation of the P-TEFb Complex by Lethal Prostate Cancer-Associated Enhancer RNAs
SRA SRP037970
BioProject PRJNA238510

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE55031_RAW.tar 697.1 Mb (http)(custom) TAR (of BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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