RNA splicing junction landscape reveals abundant tumor-specific transcripts in human cancer

Summary: RNA splicing is a critical process governing gene expression and transcriptomic diversity. Despite its importance, a detailed examination of transcript variation at the splicing junction level remains scarce. Here, we perform a thorough analysis of RNA splicing junctions in 34,775 samples a...

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Main Authors: Qin Li, Ziteng Li, Bing Chen, Jingjing Zhao, Hongwu Yu, Jia Hu, Hongyan Lai, Hena Zhang, Yan Li, Zhiqiang Meng, Zhixiang Hu, Shenglin Huang
Format: Article
Language:English
Published: Elsevier 2024-11-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124724012440
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author Qin Li
Ziteng Li
Bing Chen
Jingjing Zhao
Hongwu Yu
Jia Hu
Hongyan Lai
Hena Zhang
Yan Li
Zhiqiang Meng
Zhixiang Hu
Shenglin Huang
author_facet Qin Li
Ziteng Li
Bing Chen
Jingjing Zhao
Hongwu Yu
Jia Hu
Hongyan Lai
Hena Zhang
Yan Li
Zhiqiang Meng
Zhixiang Hu
Shenglin Huang
author_sort Qin Li
collection DOAJ
description Summary: RNA splicing is a critical process governing gene expression and transcriptomic diversity. Despite its importance, a detailed examination of transcript variation at the splicing junction level remains scarce. Here, we perform a thorough analysis of RNA splicing junctions in 34,775 samples across multiple sample types. We identified 29,051 tumor-specific transcripts (TSTs) in pan-cancer, with a majority of these TSTs being unannotated. Our findings show that TSTs are positively correlated with tumor stemness and linked to unfavorable outcomes in cancer patients. Additionally, TSTs display mutual exclusivity with somatic mutations and are overrepresented in transposable-element-derived transcripts possessing oncogenic functions. Importantly, TSTs can generate putative neoantigens for immunotherapy. Moreover, TSTs can be detected in blood extracellular vesicles from cancer patients. Our results shed light on the intricacies of RNA splicing and offer promising avenues for cancer diagnosis and therapy.
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spelling doaj-art-a614c04e998f41fbae9f973e3d07285a2025-08-20T01:54:15ZengElsevierCell Reports2211-12472024-11-01431111489310.1016/j.celrep.2024.114893RNA splicing junction landscape reveals abundant tumor-specific transcripts in human cancerQin Li0Ziteng Li1Bing Chen2Jingjing Zhao3Hongwu Yu4Jia Hu5Hongyan Lai6Hena Zhang7Yan Li8Zhiqiang Meng9Zhixiang Hu10Shenglin Huang11Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Pathology, Fudan University Shanghai Cancer Center, and Institute of Pathology, Fudan University, Shanghai 200032, ChinaDepartment of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaDepartment of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaDepartment of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaDepartment of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaDepartment of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaDepartment of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaDepartment of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaDepartment of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaDepartment of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Corresponding authorDepartment of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Corresponding authorDepartment of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Corresponding authorSummary: RNA splicing is a critical process governing gene expression and transcriptomic diversity. Despite its importance, a detailed examination of transcript variation at the splicing junction level remains scarce. Here, we perform a thorough analysis of RNA splicing junctions in 34,775 samples across multiple sample types. We identified 29,051 tumor-specific transcripts (TSTs) in pan-cancer, with a majority of these TSTs being unannotated. Our findings show that TSTs are positively correlated with tumor stemness and linked to unfavorable outcomes in cancer patients. Additionally, TSTs display mutual exclusivity with somatic mutations and are overrepresented in transposable-element-derived transcripts possessing oncogenic functions. Importantly, TSTs can generate putative neoantigens for immunotherapy. Moreover, TSTs can be detected in blood extracellular vesicles from cancer patients. Our results shed light on the intricacies of RNA splicing and offer promising avenues for cancer diagnosis and therapy.http://www.sciencedirect.com/science/article/pii/S2211124724012440CP: Cell biologyCP: Molecular biology
spellingShingle Qin Li
Ziteng Li
Bing Chen
Jingjing Zhao
Hongwu Yu
Jia Hu
Hongyan Lai
Hena Zhang
Yan Li
Zhiqiang Meng
Zhixiang Hu
Shenglin Huang
RNA splicing junction landscape reveals abundant tumor-specific transcripts in human cancer
Cell Reports
CP: Cell biology
CP: Molecular biology
title RNA splicing junction landscape reveals abundant tumor-specific transcripts in human cancer
title_full RNA splicing junction landscape reveals abundant tumor-specific transcripts in human cancer
title_fullStr RNA splicing junction landscape reveals abundant tumor-specific transcripts in human cancer
title_full_unstemmed RNA splicing junction landscape reveals abundant tumor-specific transcripts in human cancer
title_short RNA splicing junction landscape reveals abundant tumor-specific transcripts in human cancer
title_sort rna splicing junction landscape reveals abundant tumor specific transcripts in human cancer
topic CP: Cell biology
CP: Molecular biology
url http://www.sciencedirect.com/science/article/pii/S2211124724012440
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