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GEO help: Mouse over screen elements for information. |
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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
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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.
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Overall design |
ChIP-Seq analysis of PDAC and PDAC cell lines.
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Contributor(s) |
Yu RT, Antal C, Evans RM |
Citation(s) |
37673892 |
BioProject |
PRJNA678286 |
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Submission date |
Jun 05, 2023 |
Last update date |
Sep 15, 2023 |
Contact name |
Ruth T Yu |
Organization name |
Salk Institute
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Department |
Gene Expression Lab
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Lab |
Ronald Evans
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Street address |
10010 N Torrey Pines Rd
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City |
La Jolla |
State/province |
CA |
ZIP/Postal code |
92037 |
Country |
USA |
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Platforms (2) |
GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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Samples (24)
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GSM7445276 |
PDAC, EtOH, 24 hrs, ERalpha ab |
GSM7445277 |
PDAC, 4-OHT, 6 hrs, Myc ab |
GSM7445278 |
PDAC, 4-OHT, 6 hrs, ERalpha ab |
GSM7445279 |
PDAC, EtOH, 6 hrs, Myc ab |
GSM7445280 |
PDAC, EtOH, 6 hrs, ERalpha ab |
GSM7445281 |
YAPC, H3K27Ac |
GSM7445282 |
Mutj, H3K27Ac |
GSM7445283 |
CAPAN1, H3K27Ac |
GSM7445284 |
CAPAN2, H3K27Ac |
GSM7445285 |
PaTu8988T, H3K27Ac |
GSM7445286 |
PaTu8902, H3K27Ac |
GSM7445287 |
KCIMOH1, H3K27Ac |
GSM7445288 |
HupT4, H3K27Ac |
GSM7445289 |
HS766T, H3K27Ac |
GSM7445290 |
Panc1, H3K27Ac |
GSM7445291 |
Panc02, 03, H3K27Ac |
GSM7445292 |
Panc03, 27, H3K27Ac |
GSM7445293 |
MiaPaca2, H3K27Ac |
GSM7445294 |
AA0779E, H3K27Ac |
GSM7445295 |
SU86, 86, H3K27Ac |
GSM7445296 |
PSN1, H3K27Ac |
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Supplementary file |
Size |
Download |
File type/resource |
GSE234078_RAW.tar |
881.9 Mb |
(http)(custom) |
TAR (of BED, BEDGRAPH) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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