Widespread and Functional RNA Circularization in Localized Prostate Cancer

Sujun Chen; Vincent Huang; Xin Xu; Julie Livingstone; Fraser Soares; Jouhyun Jeon; Yong Zeng; Junjie Tony Hua; Jessica Petricca; Haiyang Guo; Miranda Wang; Fouad Yousif; Yuzhe Zhang; Nilgun Donmez; Musaddeque Ahmed; Stas Volik; Anna Lapuk; Melvin L.K. Chua; Lawrence E. Heisler; Adrien Foucal; Natalie S. Fox; Michael Fraser; Vinayak Bhandari; Yu Jia Shiah; Jiansheng Guan; Jixi Li; Michèle Orain; Valérie Picard; Hélène Hovington; Alain Bergeron; Louis Lacombe; Yves Fradet; Bernard Têtu; Stanley Liu; Felix Feng; Xue Wu; Yang W. Shao; Malgorzata A. Komor; Cenk Sahinalp; Colin Collins; Youri Hoogstrate; Mark de Jong; Remond J.A. Fijneman; Teng Fei; Guido Jenster; Theodorus van der Kwast; Robert G. Bristow; Paul C. Boutros; Housheng Hansen He

doi:10.1016/j.cell.2019.01.025

Widespread and Functional RNA Circularization in Localized Prostate Cancer

Sujun Chen, Vincent Huang, Xin Xu, Julie Livingstone, Fraser Soares, Jouhyun Jeon, Yong Zeng, Junjie Tony Hua, Jessica Petricca, Haiyang Guo, Miranda Wang, Fouad Yousif, Yuzhe Zhang, Nilgun Donmez, Musaddeque Ahmed, Stas Volik, Anna Lapuk, Melvin L.K. Chua, Lawrence E. Heisler, Adrien FoucalNatalie S. Fox, Michael Fraser, Vinayak Bhandari, Yu Jia Shiah, Jiansheng Guan, Jixi Li, Michèle Orain, Valérie Picard, Hélène Hovington, Alain Bergeron, Louis Lacombe, Yves Fradet, Bernard Têtu, Stanley Liu, Felix Feng, Xue Wu, Yang W. Shao, Malgorzata A. Komor, Cenk Sahinalp, Colin Collins, Youri Hoogstrate, Mark de Jong, Remond J.A. Fijneman, Teng Fei, Guido Jenster, Theodorus van der Kwast, Robert G. Bristow, Paul C. Boutros, Housheng Hansen He

Research output: Contribution to journal › Article › peer-review

Abstract

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 ∼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.

Original language	English
Pages (from-to)	831-843.e22
Journal	Cell
Volume	176
Issue number	4
Early online date	7 Feb 2019
DOIs	https://doi.org/10.1016/j.cell.2019.01.025
Publication status	Published - 2019

Keywords

biomarker
circular RNA
non-coding RNA
prostate cancer
RNA-seq
transcriptome

Research Beacons, Institutes and Platforms

Manchester Cancer Research Centre

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cell.2019.01.025

Cite this

Chen, S., Huang, V., Xu, X., Livingstone, J., Soares, F., Jeon, J., Zeng, Y., Hua, J. T., Petricca, J., Guo, H., Wang, M., Yousif, F., Zhang, Y., Donmez, N., Ahmed, M., Volik, S., Lapuk, A., Chua, M. L. K., Heisler, L. E., ... He, H. H. (2019). Widespread and Functional RNA Circularization in Localized Prostate Cancer. Cell, 176(4), 831-843.e22. https://doi.org/10.1016/j.cell.2019.01.025

@article{59b32d01e0de418787fa48ab1014f9fd,

title = "Widespread and Functional RNA Circularization in Localized Prostate Cancer",

abstract = "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 ∼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.",

keywords = "biomarker, circular RNA, non-coding RNA, prostate cancer, RNA-seq, transcriptome",

author = "Sujun Chen and Vincent Huang and Xin Xu and Julie Livingstone and Fraser Soares and Jouhyun Jeon and Yong Zeng and Hua, {Junjie Tony} and Jessica Petricca and Haiyang Guo and Miranda Wang and Fouad Yousif and Yuzhe Zhang and Nilgun Donmez and Musaddeque Ahmed and Stas Volik and Anna Lapuk and Chua, {Melvin L.K.} and Heisler, {Lawrence E.} and Adrien Foucal and Fox, {Natalie S.} and Michael Fraser and Vinayak Bhandari and Shiah, {Yu Jia} and Jiansheng Guan and Jixi Li and Mich{\`e}le Orain and Val{\'e}rie Picard and H{\'e}l{\`e}ne Hovington and Alain Bergeron and Louis Lacombe and Yves Fradet and Bernard T{\^e}tu and Stanley Liu and Felix Feng and Xue Wu and Shao, {Yang W.} and Komor, {Malgorzata A.} and Cenk Sahinalp and Colin Collins and Youri Hoogstrate and {de Jong}, Mark and Fijneman, {Remond J.A.} and Teng Fei and Guido Jenster and {van der Kwast}, Theodorus and Bristow, {Robert G.} and Boutros, {Paul C.} and He, {Housheng Hansen}",

year = "2019",

doi = "10.1016/j.cell.2019.01.025",

language = "English",

volume = "176",

pages = "831--843.e22",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "4",

}

Chen, S, Huang, V, Xu, X, Livingstone, J, Soares, F, Jeon, J, Zeng, Y, Hua, JT, Petricca, J, Guo, H, Wang, M, Yousif, F, Zhang, Y, Donmez, N, Ahmed, M, Volik, S, Lapuk, A, Chua, MLK, Heisler, LE, Foucal, A, Fox, NS, Fraser, M, Bhandari, V, Shiah, YJ, Guan, J, Li, J, Orain, M, Picard, V, Hovington, H, Bergeron, A, Lacombe, L, Fradet, Y, Têtu, B, Liu, S, Feng, F, Wu, X, Shao, YW, Komor, MA, Sahinalp, C, Collins, C, Hoogstrate, Y, de Jong, M, Fijneman, RJA, Fei, T, Jenster, G, van der Kwast, T, Bristow, RG, Boutros, PC & He, HH 2019, 'Widespread and Functional RNA Circularization in Localized Prostate Cancer', Cell, vol. 176, no. 4, pp. 831-843.e22. https://doi.org/10.1016/j.cell.2019.01.025

TY - JOUR

T1 - Widespread and Functional RNA Circularization in Localized Prostate Cancer

AU - Chen, Sujun

AU - Huang, Vincent

AU - Xu, Xin

AU - Livingstone, Julie

AU - Soares, Fraser

AU - Jeon, Jouhyun

AU - Zeng, Yong

AU - Hua, Junjie Tony

AU - Petricca, Jessica

AU - Guo, Haiyang

AU - Wang, Miranda

AU - Yousif, Fouad

AU - Zhang, Yuzhe

AU - Donmez, Nilgun

AU - Ahmed, Musaddeque

AU - Volik, Stas

AU - Lapuk, Anna

AU - Chua, Melvin L.K.

AU - Heisler, Lawrence E.

AU - Foucal, Adrien

AU - Fox, Natalie S.

AU - Fraser, Michael

AU - Bhandari, Vinayak

AU - Shiah, Yu Jia

AU - Guan, Jiansheng

AU - Li, Jixi

AU - Orain, Michèle

AU - Picard, Valérie

AU - Hovington, Hélène

AU - Bergeron, Alain

AU - Lacombe, Louis

AU - Fradet, Yves

AU - Têtu, Bernard

AU - Liu, Stanley

AU - Feng, Felix

AU - Wu, Xue

AU - Shao, Yang W.

AU - Komor, Malgorzata A.

AU - Sahinalp, Cenk

AU - Collins, Colin

AU - Hoogstrate, Youri

AU - de Jong, Mark

AU - Fijneman, Remond J.A.

AU - Fei, Teng

AU - Jenster, Guido

AU - van der Kwast, Theodorus

AU - Bristow, Robert G.

AU - Boutros, Paul C.

AU - He, Housheng Hansen

PY - 2019

Y1 - 2019

N2 - 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 ∼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.

AB - 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 ∼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.

KW - biomarker

KW - circular RNA

KW - non-coding RNA

KW - prostate cancer

KW - RNA-seq

KW - transcriptome

U2 - 10.1016/j.cell.2019.01.025

DO - 10.1016/j.cell.2019.01.025

M3 - Article

C2 - 30735634

AN - SCOPUS:85060759325

SN - 0092-8674

VL - 176

SP - 831-843.e22

JO - Cell

JF - Cell

IS - 4

ER -

Widespread and Functional RNA Circularization in Localized Prostate Cancer

Abstract

Keywords

Research Beacons, Institutes and Platforms

UN SDGs

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