A widespread length-dependent splicing dysregulation in cancer.
dc.contributor.author | Zhang, Sirui | |
dc.contributor.author | Mao, Miaowei | |
dc.contributor.author | Lv, Yuesheng | |
dc.contributor.author | Yang, Yingqun | |
dc.contributor.author | He, Weijing | |
dc.contributor.author | Song, Yongmei | |
dc.contributor.author | Wang, Yongbo | |
dc.contributor.author | Yang, Yun | |
dc.contributor.author | Al Abo, Muthana | |
dc.contributor.author | Freedman, Jennifer A | |
dc.contributor.author | Patierno, Steven R | |
dc.contributor.author | Wang, Yang | |
dc.contributor.author | Wang, Zefeng | |
dc.date.accessioned | 2022-10-04T20:25:10Z | |
dc.date.available | 2022-10-04T20:25:10Z | |
dc.date.issued | 2022-08 | |
dc.date.updated | 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 | |
dc.identifier.issn | 2375-2548 | |
dc.identifier.uri | ||
dc.language | eng | |
dc.publisher | American Association for the Advancement of Science (AAAS) | |
dc.relation.ispartof | Science advances | |
dc.relation.isversionof | 10.1126/sciadv.abn9232 | |
dc.subject | Humans | |
dc.subject | Neoplasms | |
dc.subject | Alternative Splicing | |
dc.subject | Reading Frames | |
dc.subject | Exons | |
dc.subject | Transcriptome | |
dc.title | A widespread length-dependent splicing dysregulation in cancer. | |
dc.type | Journal article | |
duke.contributor.orcid | Patierno, Steven R|0000-0003-0636-2128 | |
pubs.begin-page | eabn9232 | |
pubs.issue | 33 | |
pubs.organisational-group | Duke | |
pubs.organisational-group | School of Medicine | |
pubs.organisational-group | Basic Science Departments | |
pubs.organisational-group | Clinical Science Departments | |
pubs.organisational-group | Institutes and Centers | |
pubs.organisational-group | Pharmacology & Cancer Biology | |
pubs.organisational-group | Family Medicine and Community Health | |
pubs.organisational-group | Medicine | |
pubs.organisational-group | Medicine, Medical Oncology | |
pubs.organisational-group | Duke Cancer Institute | |
pubs.organisational-group | Institutes and Provost's Academic Units | |
pubs.organisational-group | University Institutes and Centers | |
pubs.organisational-group | Duke - Margolis Center for Health Policy | |
pubs.publication-status | Published | |
pubs.volume | 8 |
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