PXD030423 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | A super-enhancer regulated RNA-binding protein cascade drives pancreatic cancer |
Description | Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy in need of new therapeutic options. Using an unbiased analysis of super-enhancers (SEs) as sentinels of core genes involved in cell-specific function, we uncover a druggable SE-mediated RNA-binding protein (RBP) cascade that supports PDAC growth through enhanced mRNA translation. This cascade is driven by a SE associated with the RBP heterogeneous nuclear ribonucleoprotein F, which stabilizes protein arginine methyltransferase 1 (PRMT1) to, in turn, control the translational mediator ubiquitin-associated protein 2-like. All three of these genes and the regulatory SE are essential for PDAC growth and coordinately regulated by the Myc oncogene. In line with this, modulation of the RBP network by PRMT1 inhibition reveals a unique vulnerability in Myc-high PDAC patient organoids and markedly reduces tumor growth in vivo. Our study highlights a functional link between epigenetic regulation and mRNA translation and identifies components that comprise unexpected therapeutic targets for PDAC. |
HostingRepository | PRIDE |
AnnounceDate | 2023-06-15 |
AnnouncementXML | Submission_2023-06-15_02:32:57.797.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD030423 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | JoleneDiedrich |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | dimethylated residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-12-15 08:13:00 | ID requested | |
⏵ 1 | 2023-06-15 02:32:58 | announced | |
Publication List
Keyword List
submitter keyword: PRMT1,RNA-binding protein, Pancreatic cancer, super-enhancers, tumor growth |
Contact List
Ronald M.Evans |
contact affiliation | Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA |
contact email | evans@salk.edu |
lab head | |
JoleneDiedrich |
contact affiliation | Salk |
contact email | jdiedrich@salk.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD030423
- Label: PRIDE project
- Name: A super-enhancer regulated RNA-binding protein cascade drives pancreatic cancer