A widespread length-dependent splicing dysregulation in cancer.

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Zhang, Sirui

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Mao, Miaowei

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Lv, Yuesheng

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Yang, Yingqun

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He, Weijing

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Song, Yongmei

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Wang, Yongbo

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Yang, Yun

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Al Abo, Muthana

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Freedman, Jennifer A

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Patierno, Steven R

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Wang, Yang

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Wang, Zefeng

dc.date.accessioned

2022-10-04T20:25:10Z

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2022-10-04T20:25:10Z

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2022-08

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2022-10-04T20:25:07Z

dc.description.abstract

Dysregulation of alternative splicing is a key molecular hallmark of cancer. However, the common features and underlying mechanisms remain unclear. Here, we report an intriguing length-dependent splicing regulation in cancers. By systematically analyzing the transcriptome of thousands of cancer patients, we found that short exons are more likely to be mis-spliced and preferentially excluded in cancers. Compared to other exons, cancer-associated short exons (CASEs) are more conserved and likely to encode in-frame low-complexity peptides, with functional enrichment in GTPase regulators and cell adhesion. We developed a CASE-based panel as reliable cancer stratification markers and strong predictors for survival, which is clinically useful because the detection of short exon splicing is practical. Mechanistically, mis-splicing of CASEs is regulated by elevated transcription and alteration of certain RNA binding proteins in cancers. Our findings uncover a common feature of cancer-specific splicing dysregulation with important clinical implications in cancer diagnosis and therapies.

dc.identifier.issn

2375-2548

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2375-2548

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https://hdl.handle.net/10161/26059

dc.language

eng

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American Association for the Advancement of Science (AAAS)

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Science advances

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10.1126/sciadv.abn9232

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Humans

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Neoplasms

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Alternative Splicing

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Reading Frames

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Exons

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Transcriptome

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A widespread length-dependent splicing dysregulation in cancer.

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Journal article

duke.contributor.orcid

Patierno, Steven R|0000-0003-0636-2128

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eabn9232

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33

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Duke

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School of Medicine

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Basic Science Departments

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Clinical Science Departments

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Institutes and Centers

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Pharmacology & Cancer Biology

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Family Medicine and Community Health

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Medicine

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Medicine, Medical Oncology

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Duke Cancer Institute

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Institutes and Provost's Academic Units

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University Institutes and Centers

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Duke - Margolis Center for Health Policy

pubs.publication-status

Published

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8

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