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Status |
Public on Feb 12, 2016 |
Title |
Activation of the P-TEFb Complex by Lethal Prostate Cancer-Associated Enhancer RNAs [RNA-Seq] |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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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.
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Overall design |
Total RNA sequencing of two prostate cancer cells. Data were generated by deep sequencing, in diplicate, using Illumina HiSeq 2000.
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Contributor(s) |
Huang H, Zhao Y, Wang L |
Citation(s) |
27068475, 27221037 |
Submission date |
Feb 13, 2014 |
Last update date |
Mar 27, 2020 |
Contact name |
LIGUO WANG |
E-mail(s) |
wang.liguo@mayo.edu
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Organization name |
Mayo Clinic
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Department |
Division of Computational Biology
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Street address |
200 1st St SW
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City |
Rochester |
State/province |
MN |
ZIP/Postal code |
55905 |
Country |
USA |
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Platforms (1) |
GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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Samples (4)
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This SubSeries is part of SuperSeries: |
GSE55032 |
Activation of the P-TEFb Complex by Lethal Prostate Cancer-Associated Enhancer RNAs |
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Relations |
BioProject |
PRJNA238295 |
SRA |
SRP037969 |