ArticleNature communications2023
A super-enhancer-regulated RNA-binding protein cascade drives pancreatic cancer.
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Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24citing papers in PubMed
5.1field-weighted citation impact, top 4% of its field
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- piR‑164552 promotes malignant progression in head and neck squamous cell carcinoma via the RBM4/EIF4E2 signaling axis: Insights from multi‑omics and functional analyses.International journal of oncology · 2026Article
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- Copy Number Amplification and c-Myc Transcriptional Activation-Mediated RNA-Binding Protein MEX3A Promotes EGFR-TKI Resistance in Non-Small-Cell Lung Cancer.Thoracic cancer · 2026Article
- HNRNPF Increases MAF and CCNB2 Levels To Promote Cancer Cell Stemness and Progression of Pancreatic Ductal Adenocarcinoma.Stem cell reviews and reports · 2026Article
- CRISPR screen of human pancreatic cancer xenografts identifies a KLF5 proliferation vulnerability through epigenetic modifiers NCAPD2 and MTHFD1.Molecular cancer · 2026Article
- Predictive prioritization of enhancers associated with pancreatic disease risk.Cell genomics · 2026Article
- ERK phosphorylates HNRNPF to promote the proliferation and suppress the differentiation of embryonic stem cells.Nucleic acids research · 2026Article
- Post-transcriptional regulation of mRNA stability in pancreatic ductal adenocarcinoma.Frontiers in immunology · 2026Review
- HERVH-derived eRNA activates a super-enhancer-driven ALDH1A3/SAT1 axis to promote ferroptosis escape and pancreatic cancer development.Science advances · 2025Article
- Arginine methylation in cancer: mechanisms and therapeutic implications.Biomarker research · 2025Review
- O-GlcNAcylation of UBAP2L regulates stress granule formation and sunitinib resistance in clear cell renal cell carcinoma.Journal of experimental & clinical cancer research : CR · 2025Article
- RNA binding protein DDX3X drives pancreatic cancer progression via the TLE2-MYL9 axis.Science advances · 2025Article
- PRMT1 oligomerization regulates RNA-binding protein cascade to promote pancreatic cancer.Life science alliance · 2025Article
- ASO Therapy Targeting STAU2 to Inhibit Pancreatic Ductal Adenocarcinoma Progression and Metastasis by Regulating the PALLD-Mediated EMT Signaling Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The dual role of RNA-binding proteins: promotion of tumorigenesis, drug resistance, and emerging therapeutic targets.Acta biochimica et biophysica Sinica · 2025Article
- Long Non-Coding RNAs and RNA-Binding Proteins in Pancreatic Cancer Development and Progression.Cancers · 2025Review
- Functional screen identifies RBM42 as a mediator of oncogenic mRNA translation specificity.Nature cell biology · 2025Article
- RNA binding protein Pumilio2 promotes chemoresistance of pancreatic cancer via focal adhesion pathway and interacting with transcription factor EGR1.Cellular and molecular life sciences : CMLS · 2025Article
- Super-enhancers in tumors: unraveling recent advances in their role in Oncogenesis and the emergence of targeted therapies.Journal of translational medicine · 2025Review
- SENP1 inhibits aerobic glycolysis in AβCell biology and toxicology · 2025Article
Corrections and comments
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Authors and funding
38 authors at 7 institutions in 4 countries.
Corina E AntalGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.ORCID http://orcid.org/0000-0002-6174-4930
Tae Gyu OhGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.
Stefan AignerDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
En-Ching LuoDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
Brian A YeeDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0001-5615-8550
Tania CamposThe Francis Crick Institute, 1 Midland Rd, London, NW1 1AT, UK.
Hervé TiriacMoores Cancer Center, University of California San Diego, La Jolla, CA, 92037, USA.ORCID http://orcid.org/0000-0001-5039-6750
Katherine L RothamelDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
Zhang ChengCenter for Epigenomics, University of California San Diego, La Jolla, CA, 92037, USA.
Henry JiaoCenter for Epigenomics, University of California San Diego, La Jolla, CA, 92037, USA.
Allen WangCenter for Epigenomics, University of California San Diego, La Jolla, CA, 92037, USA.
Nasun HahGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.ORCID http://orcid.org/0000-0003-1509-2799
Elizabeth LenkiewiczMayo Clinic in Arizona, Scottsdale, AZ, 85259, USA.
Jan C LumibaoRegulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.
Morgan L TruittGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.
Gabriela EstepaGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.
Ester BanayoGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.
Senada BashiGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.
Edgar EsparzaMoores Cancer Center, University of California San Diego, La Jolla, CA, 92037, USA.
Ruben M MunozMolecular Medicine Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA.
Jolene K DiedrichMass Spectrometry Core for Proteomics and Metabolomics, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.
Nicole M SodirThe Francis Crick Institute, 1 Midland Rd, London, NW1 1AT, UK.
Jasmine R MuellerDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
Cory R FraserHonorHealth Research Institute, Scottsdale, AZ, 85258, USA.
Erkut BorazanciMolecular Medicine Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA.
David PropperBarts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, USA.ORCID http://orcid.org/0000-0002-4274-5460
Daniel D Von HoffMolecular Medicine Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA.ORCID http://orcid.org/0000-0003-4723-7681
Christopher LiddleStorr Liver Centre, Westmead Institute for Medical Research and Sydney Medical School, University of Sydney, Westmead Hospital, Westmead, NSW, 2145, Australia.
Ruth T YuGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.ORCID http://orcid.org/0000-0002-9527-9627
Annette R AtkinsGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.
Haiyong HanMolecular Medicine Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA.ORCID http://orcid.org/0000-0001-9031-9880
Andrew M LowyThe Francis Crick Institute, 1 Midland Rd, London, NW1 1AT, UK.
Michael T BarrettMolecular Medicine Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA.ORCID http://orcid.org/0000-0002-5646-1530
Dannielle D EngleRegulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.
Gerard I EvanThe Francis Crick Institute, 1 Midland Rd, London, NW1 1AT, UK.ORCID http://orcid.org/0000-0003-0412-1216
Gene W YeoDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
Michael DownesGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA. downes@salk.edu.
Ronald M EvansGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA. evans@salk.edu.ORCID http://orcid.org/0000-0002-9986-5965
Salk Institute for Biological Studies · USUniversity of California San Diego · USTranslational Genomics Research Institute · USThe Francis Crick Institute · GBMayo Clinic in Arizona · USScottsdale Community College · USThe University of Sydney · AU
Funding
VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jesse Nodora · 1985 to 2026
$124.9MViral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Reuben Shaw · 1985 to 2026
$82.8MYeast Genetics and Stress Response Genes-BiomedicalP42ES010337 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TUKEY, ROBERT H · 2000 to 2022
$69.8MTranscriptional GenomicsP01HL088093 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WITZTUM, JOSEPH L. · 2008 to 2018
$26.4MProject 3: The AMPK Autophagy Pathway as a Metabolic Liability in Pancratic Ductal AdenocarcinomaP01CA265762 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI TONY R. HUNTER · 2023 to 2026
$14.6MFunctional RNA elements in the human genomeR01HG004659 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Kevin Daniel Corbett, Eugene Wei-Ming Yeo · 2008 to 2026
$12.4MA Comprehensive Functional Map of Human Protein-RNA InteractionsU41HG009889 · NHGRI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI GRAVELEY, BRENTON R. · 2018 to 2021
$9.4MSalk Institute Cancer Training GrantT32CA009370 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Diana Clare Hargreaves, Jan Karlseder · 1986 to 2026
$8.6MPredoctoral and Postdoctoral Training in Cancer Cell BiologyT32CA067754 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEAN Y.J. WANG · 1995 to 2026
$6.5MA comprehensive binding and functional map of human RNA-binding proteinsU24HG009889 · NHGRI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI GRAVELEY, BRENTON R., YEO, EUGENE WEI-MING · 2022 to 2025
$5.5MOrganic nanoparticles for dual MRI-guided therapeutic selection and ovarian cancer drug deliveryR01CA220468 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Jeremiah Allen Johnson · 2017 to 2026
$4.9MRON Receptor in Pancreatic Cancer Biology and TherapyR01CA155620 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LOWY, ANDREW M · 2011 to 2021
$2.9MNCI NIH HHS P01 CA265762NCI NIH HHS P30 CA014195NCI NIH HHS P30 CA023100NCI NIH HHS R01 CA155620NCI NIH HHS R01 CA220468NCI NIH HHS T32 CA009370NCI NIH HHS T32 CA067754NHGRI NIH HHS R01 HG004659NHGRI NIH HHS U24 HG009889NHGRI NIH HHS U41 HG009889NHLBI NIH HHS P01 HL088093NIDDK NIH HHS R01 DK057978NIEHS NIH HHS P42 ES010337
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy in need of new therapeutic options. Using unbiased analyses of super-enhancers (SEs) as sentinels of core genes involved in cell-specific function, here 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 male mice. Our study highlights a functional link between epigenetic regulation and mRNA translation and identifies components that comprise unexpected therapeutic targets for PDAC.
Indexed as
Carcinoma, Pancreatic DuctalPancreatic NeoplasmsAnimalsEpigenesis, GeneticMaleMethyltransferasesMiceRegulatory Sequences, Nucleic AcidRNARNA-Binding ProteinsMethyltransferasesRNARNA-Binding Proteins
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.