PXD030423

PXD030423 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-15 08:13:00	ID requested
⏵ 1	2023-06-15 02:32:58	announced

10.6019/PXD030423;

submitter keyword: PRMT1,RNA-binding protein, Pancreatic cancer, super-enhancers, tumor growth

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

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PRIDE project URI

• PRIDE
  1. PXD030423
     1. Label: PRIDE project
     2. Name: A super-enhancer regulated RNA-binding protein cascade drives pancreatic cancer