The Landscape of Circular RNA in Cancer

• Published in: Cell 2019-02, Vol.176 (4), p.869-881.e13
• Main Authors: Vo, Josh N., Cieslik, Marcin, Zhang, Yajia, Shukla, Sudhanshu, Xiao, Lanbo, Zhang, Yuping, Wu, Yi-Mi, Dhanasekaran, Saravana M., Engelke, Carl G., Cao, Xuhong, Robinson, Dan R., Nesvizhskii, Alexey I., Chinnaiyan, Arul M.
• Format: Article
• Language: English
• Subjects: biomarkers; Biomarkers, Tumor - genetics; cancer; circRNA; circRNA database; Databases, Genetic; exome capture sequencing; Exome Sequencing - methods; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic - genetics; High-Throughput Nucleotide Sequencing; Humans; MicroRNAs - genetics; Neoplasms - genetics; non-coding RNA; read-through transcripts; RNA - genetics; RNA - metabolism; RNA, Circular; Sequence Analysis, RNA - methods
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2018.12.021

Circular RNAs (circRNAs) are an intriguing class of RNA due to their covalently closed structure, high stability, and implicated roles in gene regulation. Here, we used an exome capture RNA sequencing protocol to detect and characterize circRNAs across >2,000 cancer samples. When compared against Ribo-Zero and RNase R, capture sequencing significantly enhanced the enrichment of circRNAs and preserved accurate circular-to-linear ratios. Using capture sequencing, we built the most comprehensive catalog of circRNA species to date: MiOncoCirc, the first database to be composed primarily of circRNAs directly detected in tumor tissues. Using MiOncoCirc, we identified candidate circRNAs to serve as biomarkers for prostate cancer and were able to detect circRNAs in urine. We further detected a novel class of circular transcripts, termed read-through circRNAs, that involved exons originating from different genes. MiOncoCirc will serve as a valuable resource for the development of circRNAs as diagnostic or therapeutic targets across cancer types. [Display omitted] •Use of exome capture transcriptome sequencing to compile a cancer circRNA landscape•MiOncoCirc is the most comprehensive catalog of cancer-based circRNA species•MiOncoCirc contains circRNA from cancer cell lines as well as tumor samples•Novel biomarkers can be nominated through MiOncoCirc MiOncoCirc provides a reference of the circular RNA landscape across 40 cancer types.