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The landscape of alternative splicing in aggressive prostate cancers

ABSTRACT: We 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE141633 | GEO | 2019/12/10

REPOSITORIES: GEO

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