The Landscape of Circular RNA in Cancer

被引:1320
作者
Vo, Josh N. [1 ,2 ]
Cieslik, Marcin [1 ,2 ]
Zhang, Yajia [1 ,2 ]
Shukla, Sudhanshu [2 ,3 ]
Xiao, Lanbo [2 ]
Zhang, Yuping [2 ]
Wu, Yi-Mi [2 ]
Dhanasekaran, Saravana M. [2 ]
Engelke, Carl G. [2 ]
Cao, Xuhong [2 ]
Robinson, Dan R. [2 ]
Nesvizhskii, Alexey I. [1 ,2 ,4 ,6 ]
Chinnaiyan, Arul M. [1 ,2 ,4 ,5 ,6 ,7 ]
机构
[1] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA
[3] Indian Inst Technol Dharwad, Dept Biosci & Bioengn, Dharwad 580011, Karnataka, India
[4] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA
[5] Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA
[6] Univ Michigan, Rogel Canc Ctr, Ann Arbor, MI 48109 USA
[7] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA
关键词
INTEGRATIVE CLINICAL GENOMICS; LONG NONCODING RNAS; PROSTATE-CANCER; BIOGENESIS; DATABASE; SEQ; EXPRESSION; BIOMARKER; MICRORNA; FUSION;
D O I
10.1016/j.cell.2018.12.021
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:869 / +
页数:26
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