Widespread and Functional RNA Circularization in Localized Prostate Cancer

被引:350
作者
Chen, Sujun [1 ,2 ,3 ]
Huang, Vincent [3 ]
Xu, Xin [2 ]
Livingstone, Julie [3 ]
Soares, Fraser [2 ]
Jeon, Jouhyun [3 ]
Zeng, Yong [2 ]
Hua, Junjie Tony [1 ,2 ]
Petricca, Jessica [1 ,2 ]
Guo, Haiyang [2 ]
Wang, Miranda [2 ]
Yousif, Fouad [3 ]
Zhang, Yuzhe [2 ,4 ,5 ]
Donmez, Nilgun [6 ]
Ahmed, Musaddeque [2 ]
Volik, Stas [6 ]
Lapuk, Anna [6 ,33 ]
Chua, Melvin L. K. [3 ]
Heisler, Lawrence E. [3 ]
Foucal, Adrien [3 ]
Fox, Natalie S. [1 ,3 ]
Fraser, Michael [2 ,3 ]
Bhandari, Vinayak [1 ,3 ]
Shiah, Yu-Jia [3 ]
Guan, Jiansheng [2 ,7 ]
Li, Jixi [8 ,9 ]
Orain, Michele [10 ]
Picard, Valerie [10 ]
Hovington, Helene [10 ]
Bergeron, Alain [10 ]
Lacombe, Louis [10 ]
Fradet, Yves [10 ]
Tetu, Bernard [11 ]
Liu, Stanley [1 ,11 ,12 ]
Feng, Felix [13 ,14 ,15 ,16 ]
Wu, Xue [17 ]
Shao, Yang W. [17 ,18 ]
Komor, Malgorzata A. [19 ,20 ]
Sahinalp, Cenk [6 ]
Collins, Colin [6 ,21 ]
Hoogstrate, Youri [22 ]
de Jong, Mark [23 ]
Fijneman, Remond J. A. [19 ]
Fei, Teng [24 ]
Jenster, Guido [22 ]
van der Kwast, Theodorus [2 ,25 ]
Bristow, Robert G. [2 ,26 ,27 ,28 ]
Boutros, Paul C. [1 ,3 ,25 ,29 ,30 ,31 ,32 ]
He, Housheng Hansen [1 ,2 ]
机构
[1] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada
[2] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada
[3] Ontario Inst Canc Res, Toronto, ON, Canada
[4] Cent China Normal Univ, Coll Life Sci, Wuhan, Hubei, Peoples R China
[5] Dali Univ, Coll Basic Med Sci, Dali, Yunnan, Peoples R China
[6] Vancouver Prostate Ctr, Vancouver, BC, Canada
[7] Xiamen Univ Technol, Coll Elect Engn & Automat, Xiamen, Peoples R China
[8] Fudan Univ, Sch Life Sci, Dept Neurol, State Key Lab Genet Engn, Shanghai, Peoples R China
[9] Fudan Univ, Huashan Hosp, Shanghai, Peoples R China
[10] Univ Laval, CHU Quebec, Res Ctr, Quebec City, PQ, Canada
[11] Sunnybrook Hlth Sci Ctr, Sunnybrook Res Inst, Toronto, ON, Canada
[12] Sunnybrook Odette Canc Ctr, Dept Radiat Oncol, Toronto, ON, Canada
[13] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA
[14] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA
[15] Univ Calif San Francisco, Dept Med, San Francisco, CA USA
[16] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA
[17] Geneseeq Technol, Translat Med Res Inst, Toronto, ON, Canada
[18] Nanjing Med Univ, Sch Publ Hlth, Nanjing, Jiangsu, Peoples R China
[19] Netherlands Canc Inst, Dept Pathol, Translat Gastrointestinal Oncol, Amsterdam, Netherlands
[20] Vrije Univ Amsterdam, Dept Med Oncol, Med Ctr, Oncoprote Lab, Amsterdam, Netherlands
[21] Univ British Columbia, Dept Urol Sci, Vancouver, BC, Canada
[22] Erasmus MC, Dept Urol, Rotterdam, Netherlands
[23] GenomeScan, Leiden, Netherlands
[24] Northeastern Univ, Coll Life & Hlth Sci, Shenyang, Liaoning, Peoples R China
[25] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON, Canada
[26] Univ Manchester, Div Canc Sci, Manchester, Lancs, England
[27] Christie NHS Fdn Trust, Manchester, Lancs, England
[28] Manchester Canc Res Ctr, Manchester, Lancs, England
[29] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA
[30] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA
[31] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA
[32] Univ Calif Los Angeles, Inst Precis Hlth, Los Angeles, CA USA
[33] Contextual Genom, Vancouver, BC, Canada
基金
加拿大创新基金会; 加拿大自然科学与工程研究理事会;
关键词
R PACKAGE; EXPRESSION; IDENTIFICATION; PROGRESSION; METASTASIS; BIOMARKERS; ALIGNMENT; TARGET;
D O I
10.1016/j.cell.2019.01.025
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
The cancer transcriptome is remarkably complex, including low-abundance transcripts, many not polyadenylated. To fully characterize the transcriptome of localized prostate cancer, we performed ultra deep total RNA-seq on 144 tumors with rich clinical annotation. This revealed a linear transcriptomic subtype associated with the aggressive intraductal carcinoma sub-histology and a fusion profile that differentiates localized from metastatic disease. Analysis of back-splicing events showed widespread RNA circularization, with the average tumor expressing 7,232 circular RNAs (circRNAs). The degree of circRNA production was correlated to disease progression in multiple patient cohorts. Loss-of function screening identified 11.3% of highly abundant circRNAs as essential for cell proliferation; for similar to 90% of these, their parental linear transcripts were not essential. Individual circRNAs can have distinct functions, with circCSNK1G3 promoting cell growth by interacting with miR-181. These data advocate for adoption of ultra-deep RNA-seq without poly-A selection to interrogate both linear and circular transcriptomes.
引用
收藏
页码:831 / +
页数:35
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