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Status |
Public on Jun 03, 2021 |
Title |
A regulatory axis of YY1-PFKP promotes aggressive prostate tumorigenesis via potentiating tumor cell metabolism [ChIP-seq] |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Yin Yang 1 (YY1) acts as a transcription factor crucially involved in cell proliferation, differentiation and survival. We here report that YY1, through gene expression regulation, plays an important role in prostate tumorigenesis, notably in castration-resistant prostate cancer (CRPC) models. Specifically, we found that YY1 displays a significantly elevated level among primary samples from prostate cancer patients, relative to normal. Depletion of YY1 in multiple independent prostate cancer model systems dramatically reduced tumor cell growth in vitro and significantly delayed oncogenic progression in vivo. Using integrated analyses of chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq), we further defined YY1-regulated cistrome, among which include a set of metabolism-related genes such as PFKP (Phosphofructokinase, Platelet isoform), a rate-limiting enzyme essential for glycolysis. Via both gene loss-of-function and rescue studies, we demonstrate that PFKP serves as a key downstream direct target of YY1, significantly contributing to YY1-enforced oncogenic phenotypes such as enhanced tumor cell glycolysis and prostate cancer growth. Lastly, we show that BRD4, a cofactor of YY1, is critically involved in YY1-mediated activation of metabolic genes in prostate cancer cells. Altogether, this study unveils an oncogenic axis of YY1/BRD4-PFKP in prostate cancer for potentiating more aggressive tumor characteristics, which shall shed light on targeted therapy.
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Overall design |
Examination of the genome-wide binding of YY1 in prostate cancer cells .
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Contributor(s) |
Xu C, Wang GG |
Citation(s) |
33849067 |
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Submission date |
Jul 01, 2020 |
Last update date |
Jun 03, 2021 |
Contact name |
Chenxi Xu |
E-mail(s) |
[email protected]
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Phone |
9199034127
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Organization name |
University of North Carolina at Chapel Hill
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Department |
Lineberger Comprehensive Cancer Center
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Lab |
Greg Wang lab
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Street address |
450 West Drive, CB 7295, UNC cancer center, room 31-331 Chapel Hill, NC
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City |
Chapel Hill |
State/province |
North Carolina |
ZIP/Postal code |
27599 |
Country |
USA |
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Platforms (1) |
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Samples (2) |
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This SubSeries is part of SuperSeries: |
GSE153640 |
A regulatory axis of YY1-PFKP promotes aggressive prostate tumorigenesis via potentiating tumor cell metabolism |
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Relations |
BioProject |
PRJNA643527 |
SRA |
SRP269555 |
Supplementary file |
Size |
Download |
File type/resource |
GSE153639_RAW.tar |
1.3 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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