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Understanding aberrant RNA splicing to facilitate cancer diagnosis and therapy

Oncogene volume 39, pages 2231–2242 (2020)Cite this article

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Abstract

Almost all genes in normal cells undergo alternative RNA splicing to generate a greater extent of diversification of gene products for normal cellular functions. RNA splicing is tightly regulated and closely interplays with genetic and epigenetic machinery. While DNA polymorphism and somatic mutations modulate alternative splicing patterns, RNA splicing also controls genomic stability, chromatin organization, and transcriptome. Tumor cells, in turn, often take advantage of aberrant RNA splicing to develop, grow and progress into therapy-resistant tumors. Understanding alternative RNA splicing in tumor cells would, therefore, provide us opportunities to gain further insights into tumor biology, identify diagnostic or prognosis biomarkers, as well as to design effective therapeutic means to control tumor progression. Here, we provide an overview of RNA splicing mechanisms and use prostate cancer as an example to review recent advancements in our understanding of RNA splicing in cancer progression and therapy resistance. We also discuss emerging diagnostic and therapeutic potentials of RNA splicing events or RNA splicing factors.

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Fig. 1: RNA splicing regulates all steps of gene expression that are essential for normal cell functions.
Fig. 2: RNA splicing and alternative RNA splicing.
Fig. 3: SRRM4 drives AdPC progression to NEPC through regulating alternative RNA splicing.
Fig. 4: Therapeutic strategies to target RNA splicing for cancer therapy.

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Acknowledgements

This work is supported by CIHR operating grants (MOP-137007 and PJT-156150) and TFRI New Frontiers Program Grant (#1062) to XD. We thank all our formal and current lab members who contribute to various projects to understand RNA splicing in prostate cancers.

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Authors and Affiliations

  1. Department of Urologic Sciences, Faculty of Medicine, The University of British Columbia, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada

    Xuesen Dong

  2. The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada

    Xuesen Dong

  3. Faculty of Medicine, University of Toronto, 27 King’s College Circle 8, Toronto, ON, M5S 1A1, Canada

    Ruiqi Chen

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  1. Xuesen Dong
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Correspondence to Xuesen Dong.

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Dong, X., Chen, R. Understanding aberrant RNA splicing to facilitate cancer diagnosis and therapy. Oncogene 39, 2231–2242 (2020). https://doi.org/10.1038/s41388-019-1138-2

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  • DOI: https://doi.org/10.1038/s41388-019-1138-2

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