Genomics

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HNRNPM-regulated splicing dependencies in prostate cancer [RNA-Seq]


ABSTRACT: Cancer cells are differentially dependent on the splicing machinery compared to normal untransformed cells. The splicing machinery thus presents a potential therapeutic target in cancer. To identify splicing factors important for prostate cancer cell (PCa) growth, we performed an unbiased pooled shRNA screen in in vitro passaged cells and in vivo xenografted PCa tumors. Our screen revealed HNRNPM as a potential regulator of PCa cell growth. RNA- and eCLIP- sequencing data suggest that HNRNPM is bound to key homeostatic genes, and that loss of HNRNPM binding in a subset of these genes results in aberrant exon inclusion and exon back-splicing events in target transcripts. In mis-spliced transcripts, HNRNPM appears to preferentially bind to GU-rich elements in long flanking proximal introns. Mimicry of HNRNPM dependent splicing events using antisense oligonucleotides was sufficient to inhibit cell growth in HNRNPM expressing cells, suggesting that inhibition of cell growth in HNRNPM deficient cells likely has a multi-genic component. Taken together, our data reveal a role for HNRNPM in regulating PCa cell growth, and also as a potential therapeutic target in PCa. Overall design: Experiment was performed in technical triplicates of RNA isolated LNCAP cells expressing either control non-targetting shRNA (SCR) or HNRNPM targetting shRNA (2B7 or 2B9)

INSTRUMENT(S): Illumina NextSeq 500 (Homo sapiens)

ORGANISM(S): Homo sapiens  

SUBMITTER: Diana HP Low  

PROVIDER: GSE113782 | GEO | 2019-12-25

REPOSITORIES: GEO

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