Abstrakt: |
A new report from the Fred Hutchinson Cancer Research Center in Seattle, Washington explores the dysregulation of alternative polyadenylation (APA) in cancer, specifically melanoma. The researchers developed a CRISPR-Cas9-based screen to manipulate polyadenylation and measure the impact of APA events on tumor growth in mouse models. The study identifies individual APA events that control melanoma growth in mice and demonstrates concordant associations in human melanoma. For example, lengthening the 3' UTR of the Atg7 gene in mouse melanoma suppresses ATG7 protein levels, slows tumor growth, and improves host survival, which is consistent with prolonged patient survival in human melanoma cases with a long ATG7 3' UTR. This study provides a means to functionally dissect APA in physiological systems and quantifies the contributions of recurrent APA events to tumorigenic phenotypes. [Extracted from the article] |