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| Status |
Public on Nov 01, 2023 |
| Title |
Aberrant accumulation of Kras-dependent enhancer RNAs during tumor progression renders cancer cells susceptible to PAF1 depletion due to R-loop accumulation II |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Kras is the most commonly mutated oncogene in human cancer and mutant Kras is responsible for over 90% of pancreatic ductal adnocarcinoma (PDAC), the most leath cancer. Here, we identified that RNA polymerase II associated factor 1 complex (PAF1C) is specifically required for the survival of PDAC but not normal adult panreatic cells. We show that PAF1C maintains cancer cell genomic stability by restraining the over accumulation of enhancer RNAs (eRNAs) driven by mutant Kras. Loss of PAF1C leads to cancer-specific lengthening and accumulation of eRNAs on chromatin and therby abbarrent R-loop formation, TC-NER pathway activation and double stranded DNA breaks, which in turn trigger cell death. We also demonstrate that the sepcific demand for PAF1C by cancer cells is due to the global activation of enhancers and thus eRNA transcription during tumorigenesis. The work provides a novel insight in how transcription addiction is caused during tumorigenesis.
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| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for mouse pancreas with Rosa26 knockout vs. Paf1 knockout.
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| Contributor(s) |
Liu X, Liu X, Chen M |
| Citation missing |
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| |
| Submission date |
Nov 10, 2022 |
| Last update date |
Nov 01, 2023 |
| Contact name |
Xiangzheng Liu |
| E-mail(s) |
lxz19@mails.tsinghua.edu.cn
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| Organization name |
Tsinghua University
|
| Street address |
Tsinghua University, Haidian District, Beijing
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| City |
Beijing |
| ZIP/Postal code |
100084 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE217745 |
Aberrant accumulation of Kras-dependent pervasive transcripts during tumor progression renders cancer cells dependent on PAF1 expression |
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| Relations |
| BioProject |
PRJNA900250 |
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