Systematic characterization of cancer transcriptome at transcript resolution

Wei Hu, Yangjun Wu, Qili Shi, Jingni Wu, Deping Kong, Xiaohua Wu, Xianghuo He (), Teng Liu () and Shengli Li ()
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Wei Hu: Shanghai Jiao Tong University School of Medicine
Yangjun Wu: Fudan University Shanghai Cancer Center
Qili Shi: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University
Jingni Wu: Shanghai Jiao Tong University School of Medicine
Deping Kong: Shanghai Jiao Tong University School of Medicine
Xiaohua Wu: Fudan University Shanghai Cancer Center
Xianghuo He: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University
Teng Liu: Shanghai Jiao Tong University School of Medicine
Shengli Li: Shanghai Jiao Tong University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Transcribed RNAs undergo various regulation and modification to become functional transcripts. Notably, cancer transcriptome has not been fully characterized at transcript resolution. Herein, we carry out a reference-based transcript assembly across >1000 cancer cell lines. We identify 498,255 transcripts, approximately half of which are unannotated. Unannotated transcripts are closely associated with cancer-related hallmarks and show clinical significance. We build a high-confidence RNA binding protein (RBP)-transcript regulatory network, wherein most RBPs tend to regulate transcripts involved in cell proliferation. We identify numerous transcripts that are highly associated with anti-cancer drug sensitivity. Furthermore, we establish RBP-transcript-drug axes, wherein PTBP1 is experimentally validated to affect the sensitivity to decitabine by regulating KIAA1522-a6 transcript. Finally, we establish a user-friendly data portal to serve as a valuable resource for understanding cancer transcriptome diversity and its potential clinical utility at transcript level. Our study substantially extends cancer RNA repository and will facilitate anti-cancer drug discovery.

Date: 2022
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DOI: 10.1038/s41467-022-34568-z

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