A widespread length-dependent splicing dysregulation in cancer.


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.





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Publication Info

Zhang, Sirui, Miaowei Mao, Yuesheng Lv, Yingqun Yang, Weijing He, Yongmei Song, Yongbo Wang, Yun Yang, et al. (2022). A widespread length-dependent splicing dysregulation in cancer. Science advances, 8(33). p. eabn9232. 10.1126/sciadv.abn9232 Retrieved from https://hdl.handle.net/10161/26059.

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Jennifer Freedman

Associate Professor in Medicine

Steven Patierno

Charles D. Watts Distinguished Professor of Medicine

Patierno's current translational research interests are focused on the genomics molecular biology of cancer disparities, cancer biology, molecular pharmacology and targeted experimental therapeutics to control prostate, breast and lung tumor aggressiveness. He is an internationally recognized expert in cancer control, cancer causation and molecular carcinogenesis, which includes a broad spectrum of laboratory and population level research.   Patierno is also actively engaged in cancer health disparities and healthcare delivery research focused on patient navigation, survivorship, community-based interventions, mHealth, implementation sciences, cancer care economics, and policy.

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