Systematic characterization of cancer transcriptome at transcript resolution

• Published in: Nature communications 2022-11, Vol.13 (1), p.6803-6803, Article 6803
• Main Authors: Hu, Wei, Wu, Yangjun, Shi, Qili, Wu, Jingni, Kong, Deping, Wu, Xiaohua, He, Xianghuo, Liu, Teng, Li, Shengli
• Format: Article
• Language: English
• Subjects: 13/89; 38/90; 49/109; 49/88; 49/91; 5-aza-2'-deoxycytidine; 631/114/2164; 631/208/212/2019; 631/553/2711; 631/67/1059; 692/4028/67/69; Antitumor agents; Assembly; Cancer; Cell proliferation; Gene regulation; Humanities and Social Sciences; multidisciplinary; Neoplasms - drug therapy; Neoplasms - genetics; RNA - metabolism; RNA-binding protein; RNA-Binding Proteins - metabolism; Science; Science (multidisciplinary); Sensitivity; Sequence Analysis, RNA; Transcriptome - genetics; Transcriptomes; Tumor cell lines
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-34568-z

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. Modification of transcribed mRNAs enables regulation of transcription but its extent in cancer cells is incompletely understood. Here, the authors analyse transcript assembly in over 1000 cancer cell lines and find unannotated transcripts are common, and are associated with drug sensitivity.