Matches in SemOpenAlex for { <https://semopenalex.org/work/W2970887922> ?p ?o ?g. }
- W2970887922 abstract "ABSTRACT Alternative polyadenylation (APA) is a gene regulatory process that dictates mRNA 3’-UTR length, resulting in changes in mRNA stability and localization. APA is frequently disrupted in cancer and promotes tumorigenesis through altered expression of oncogenes and tumor suppressors. Pan-cancer analyses have revealed common APA events across the tumor landscape; however, little is known about tumor type-specific alterations that may uncover novel events and vulnerabilities. Here we integrate RNA-sequencing data from the Genotype-Tissue Expression (GTEx) project and The Cancer Genome Atlas (TCGA) to comprehensively analyze APA events in 148 pancreatic ductal adenocarcinomas (PDAs). We report widespread, recurrent and functionally relevant 3’-UTR alterations associated with gene expression changes of known and newly identified PDA growth-promoting genes and experimentally validate the effects of these APA events on expression. We find enrichment for APA events in genes associated with known PDA pathways, loss of tumor-suppressive miRNA binding sites, and increased heterogeneity in 3’-UTR forms of metabolic genes. Survival analyses reveal a subset of 3’-UTR alterations that independently characterize a poor prognostic cohort among PDA patients. Finally, we identify and validate the casein kinase CK1α as an APA-regulated therapeutic target in PDA. Knockdown or pharmacological inhibition of CK1α attenuates PDA cell proliferation and clonogenic growth. Our single-cancer analysis reveals APA as an underappreciated driver of pro-tumorigenic gene expression in PDA via the loss of miRNA regulation." @default.
- W2970887922 created "2019-09-05" @default.
- W2970887922 creator A5005741354 @default.
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- W2970887922 creator A5051693530 @default.
- W2970887922 creator A5063966898 @default.
- W2970887922 creator A5071953607 @default.
- W2970887922 date "2019-08-30" @default.
- W2970887922 modified "2023-09-30" @default.
- W2970887922 title "Alternative polyadenylation drives oncogenic gene expression in pancreatic ductal adenocarcinoma" @default.
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