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Series GSE234078 Query DataSets for GSE234078
Status Public on Jun 07, 2023
Title A super-enhancer regulated RNA-binding protein cascade drives pancreatic cancer
Organisms Homo sapiens; Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary We uncovered a super-enhancer (SE)-mediated pathway, integrated by Myc, that regulates protein translation to drive pancreatic tumor growth. A SE associated with heterogeneous nuclear ribonucleoprotein F (HNRNPF) controls its expression to regulate protein arginine methyltransferase 1 (PRMT1) mRNA stability. In turn, PRMT1 asymmetrically dimethylates ubiquitin-associated protein 2-like (UBAP2L) to mediate protein translation and thus tumor growth. Deletion of any of these 3 genes, or of the super-enhancer itself, all lead to a drastic reduction in tumor burden in orthotopic PDAC models. Inhibition of PRMT1 induces apoptosis and significantly reduces tumor growth. This unexpected role of HNRNPF, PRMT1 and UBAP2L in regulating tumorigenesis by coordinating protein translation underpins this pathway, downstream of Myc, as a potential therapeutic target for PDAC.
 
Overall design ChIP-Seq analysis of PDAC and PDAC cell lines.
 
Contributor(s) Yu RT, Antal C, Evans RM
Citation(s) 37673892
BioProject PRJNA678286
Submission date Jun 05, 2023
Last update date Sep 15, 2023
Contact name Ruth T Yu
Organization name Salk Institute
Department Gene Expression Lab
Lab Ronald Evans
Street address 10010 N Torrey Pines Rd
City La Jolla
State/province CA
ZIP/Postal code 92037
Country USA
 
Platforms (2)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (24)
GSM7445273 PDAC, 4-OHT, 24 hrs, Myc ab
GSM7445274 PDAC, 4-OHT, 24 hrs, ERalpha ab
GSM7445275 PDAC, EtOH, 24 hrs, Myc ab

Download family Format
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE234078_RAW.tar 881.9 Mb (http)(custom) TAR (of BED, BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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