GSE141633 The landscape of alternative splicing in aggressive prostate cancers

Contributors : John W Phillips ; Yang Pan ; Brandon L Tsai ; Zhijie Xie ; Levon Demirdjian ; Wen Xiao ; Harry T Yang ; Yida Zhang ; Chia H Lin ; Donghui Cheng ; Douglas L Black ; Owen N Witte ; Yi XingSeries Type : Expression profiling by high throughput sequencing ; Third-party reanalysisOrganism : Homo sapiensWe sought to define the landscape of alternative pre-mRNA splicing in prostate cancers and the relationship of exon choice to known genetic driver alterations. To do so, we compiled a meta-dataset comprised of RNA-Seq samples from publicly available sources representing a range of phenotypes from normal tissue to drug resistant metastases. We subjected these samples to exon-level analysis with purpose-built software. We then correlated transcriptional signatures of cancer driver pathways with these alternative splicing events and discovered that Myc signaling was correlated with incorporation of a set of cassette exons found in RNA binding proteins. We experimentally verified this finding in a human prostate cell transformation assay. Our results connect changes in alternative pre-mRNA splicing to oncogenic alterations common in prostate and many other cancers. We also establish a role for Myc in regulating RNA processing by controlling the incorporation of nonsense mediated decay-determinant exons in RNA binding proteins.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Third-party reanalysis Homo sapiens Source Type: research