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Series GSE217741 Query DataSets for GSE217741
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
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.
Overall design Comparative gene expression profiling analysis of RNA-seq data for mouse pancreas with Rosa26 knockout vs. Paf1 knockout.
Contributor(s) Liu X, Liu X, Chen M
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Submission date Nov 10, 2022
Last update date Nov 01, 2023
Contact name Xiangzheng Liu
Organization name Tsinghua University
Street address Tsinghua University, Haidian District, Beijing
City Beijing
ZIP/Postal code 100084
Country China
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (4)
GSM6725670 normal pancreas, Rosa26 knockout rep1
GSM6725671 normal pancreas, Rosa26 knockout rep2
GSM6725672 normal pancreas, Paf1 knockout rep1
This SubSeries is part of SuperSeries:
GSE217745 Aberrant accumulation of Kras-dependent pervasive transcripts during tumor progression renders cancer cells dependent on PAF1 expression
BioProject PRJNA900250

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Supplementary file Size Download File type/resource
GSE217741_All_sample_gene_name.counts.txt.gz 4.6 Mb (ftp)(http) TXT
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