MYC directs splicing changes in prostate cancers

What is it about?

The MYC oncogene stimulates cancer cell growth and has wide ranging effects on cellular gene expression, including influencing pre-mRNA splicing to alter the mRNA and protein products of many genes. We found that the alternative splicing of another oncogene, HRAS, is controlled by MYC in many cancer types. Two RNA binding proteins, hnRNPs H and F, were identified to play essential roles promoting splicing of one HRAS isoform by binding to special regulatory sequences within the HRAS pre-mRNA. Interestingly, across many cancers, expression hnRNP H and F correlate with MYC activity, but in opposite directions. Removal of hnRNP H and F from prostate cancer cells was found alter cell growth and lead to cell death.

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Photo by Milad Fakurian on Unsplash

Photo by Milad Fakurian on Unsplash

Why is it important?

MYC oncogene contributes to more than fifty percent of human cancers and is known to alter the pre-mRNA splicing reaction. However, it is not well understood how MYC specifically directs splicing changes. In this study, we used computational analyses to identify regulators of the MYC-dependent splicing in the HRAS oncogene. We then applied antisense oligonucleotide technology to delineate where these regulators act on the HRAS RNA. Overall, this study provides insights into MYC’s impact on splicing and point to possible therapeutic targets in prostate cancers.