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A super-enhancer regulated RNA-binding protein cascade drives pancreatic cancer

GSE234078 Homo sapiens; Mus musculus Genome binding/occupancy profiling by high throughput sequencing 24 samples Submitted 2023/06/07 Platform GPL20301Platform GPL21103
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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Also filed as BioProject PRJNA678286 and SRA study SRP296872. Searching any of these in the dataset finder brings you back here.

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