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Alternative Splicing: Expanding the Landscape of Cancer Biomarkers and Therapeutics.


ABSTRACT: Alternative splicing (AS) is a critical post-transcriptional regulatory mechanism used by more than 95% of transcribed human genes and responsible for structural transcript variation and proteome diversity. In the past decade, genome-wide transcriptome sequencing has revealed that AS is tightly regulated in a tissue- and developmental stage-specific manner, and also frequently dysregulated in multiple human cancer types. It is currently recognized that splicing defects, including genetic alterations in the spliced gene, altered expression of both core components or regulators of the precursor messenger RNA (pre-mRNA) splicing machinery, or both, are major drivers of tumorigenesis. Hence, in this review we provide an overview of our current understanding of splicing alterations in cancer, and emphasize the need to further explore the cancer-specific splicing programs in order to obtain new insights in oncology. Furthermore, we also discuss the recent advances in the identification of dysregulated splicing signatures on a genome-wide scale and their potential use as biomarkers. Finally, we highlight the therapeutic opportunities arising from dysregulated splicing and summarize the current approaches to therapeutically target AS in cancer.

SUBMITTER: Bessa C 

PROVIDER: S-EPMC7729450 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Alternative Splicing: Expanding the Landscape of Cancer Biomarkers and Therapeutics.

Bessa Cláudia C   Matos Paulo P   Jordan Peter P   Gonçalves Vânia V  

International journal of molecular sciences 20201127 23


Alternative splicing (AS) is a critical post-transcriptional regulatory mechanism used by more than 95% of transcribed human genes and responsible for structural transcript variation and proteome diversity. In the past decade, genome-wide transcriptome sequencing has revealed that AS is tightly regulated in a tissue- and developmental stage-specific manner, and also frequently dysregulated in multiple human cancer types. It is currently recognized that splicing defects, including genetic alterat  ...[more]

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