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| Status |
Public on Jan 20, 2020 |
| Title |
p53 activates the long noncoding RNA Pvt1b to inhibit Myc and suppress tumorigenesis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The tumor suppressor p53 transcriptionally activates target genes to suppress cellular proliferation during stress. p53 has also been implicated in the repression of the proto-oncogene Myc, but the mechanism has remained unclear. Here, we identify Pvt1b, a p53-dependent isoform of the long noncoding RNA (lncRNA) Pvt1, expressed 50 Kb downstream of Myc, which becomes induced by DNA damage or oncogenic signaling and accumulates near its site of transcription. We show that production of the Pvt1b RNA is necessary and sufficient to suppress Myc transcription in cis without altering the chromatin organization of the locus. Inhibition of Pvt1b increases Myc levels and transcriptional activity and promotes cellular proliferation. Furthermore, Pvt1b loss accelerates tumor growth, but not tumor progression, in an autochthonous mouse model of lung cancer. These findings demonstrate that Pvt1b acts at the intersection of the p53 and Myc transcriptional networks to reinforce the anti-proliferative activities of p53.
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| Overall design |
RNA isolated from mouse lung adenocarcinoma (K-rasLA2-G12D/+; p53LSL/LSL; Rosa26-CreERT2+, KPR) cells previously infected with a sgRNA targeting the Pvt1 p53RE (gΔRE) or a control sgRNA (gCon) +/- tamoxifen treatment and +/- s4U feed was subjected to oxidative-nucleophilic-aromatic-substitution chemistry and sequenced. All sequencing for experimental samples was performed in duplicate per condition assessed, while negative controls were performed as single replicates without s4U treatment.
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| Contributor(s) |
Dimitrova N, Simon M |
| Citation(s) |
31973890 |
| |
| Submission date |
Dec 30, 2019 |
| Last update date |
Apr 22, 2020 |
| Contact name |
Matthew Simon |
| E-mail(s) |
matthew.simon@yale.edu
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| Organization name |
Yale University
|
| Department |
MBB
|
| Lab |
Simon Lab
|
| Street address |
West Campus, 100 West Campus Drive, Ste MIC312A
|
| City |
Orange |
| State/province |
CT |
| ZIP/Postal code |
06477 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (19)
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| This SubSeries is part of SuperSeries: |
| GSE143204 |
p53 activates the long noncoding RNA Pvt1b to inhibit Myc and suppress tumorigenesis |
|
| Relations |
| BioProject |
PRJNA598241 |
| SRA |
SRP239126 |
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