GSE234078
GSE GEOA super-enhancer regulated RNA-binding protein cascade drives pancreatic cancer
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.
Analysis (3 steps)
View Data Processing- For human samples, reads were aligned using Bowtie2 to GRCh37 and SE peaks were called using HOMER v4.11.1 default settings (-style super, Fold change >4, p-value <0.0001).
- For mouse samples, reads were aligned using Bowtie2 to MGSCv37 (mm9) and differential peaks were called using HOMERâs79 default settings (Fold change >4, p-value <0.0001) using '-style factor'.
- Data tracks were visualized using IGV v2.3.90.