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A widespread length-dependent splicing dysregulation in cancer.
Zhang, Sirui; Mao, Miaowei; Lv, Yuesheng; Yang, Yingqun; He, Weijing; Song, Yongmei; Wang, Yongbo; Yang, Yun; Al Abo, Muthana; Freedman, Jennifer A; Patierno, Steven R; Wang, Yang; Wang, Zefeng.
Afiliación
  • Zhang S; CAS Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
  • Mao M; CAS Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
  • Lv Y; Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.
  • Yang Y; CAS Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
  • He W; Shanghai Tech University, Shanghai 200031, China.
  • Song Y; Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
  • Wang Y; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • Yang Y; State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
  • Al Abo M; Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
  • Freedman JA; CAS Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
  • Patierno SR; Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710, USA.
  • Wang Y; Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710, USA.
  • Wang Z; Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Sci Adv ; 8(33): eabn9232, 2022 08 19.
Article en En | MEDLINE | ID: mdl-35977015
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Empalme Alternativo / Neoplasias Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Sci Adv Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Empalme Alternativo / Neoplasias Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Sci Adv Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos