Widespread and Functional RNA Circularization in Localized Prostate Cancer.

Gene Expression Profiling / methods Genetic Profile HEK293 Cells Humans Male MicroRNAs / metabolism Prostate / metabolism Prostatic Neoplasms / genetics RNA / genetics RNA Splicing / genetics RNA, Circular RNA, Untranslated / genetics Sequence Analysis, RNA / methods Transcriptome
RNA-seq biomarker circular RNA non-coding RNA prostate cancer transcriptome

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
07 02 2019
Historique:
received: 17 05 2018
revised: 19 10 2018
accepted: 11 01 2019
entrez: 9 2 2019
pubmed: 9 2 2019
medline: 4 12 2019
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.cell.2019.01.025 PMID: 30735634
pubmed: 30735634
pii: S0092-8674(19)30058-3
doi: 10.1016/j.cell.2019.01.025
pii:
doi:

Substances chimiques

MicroRNAs 0
RNA, Circular 0
RNA, Untranslated 0
RNA 63231-63-0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

831-843.e22

Subventions

Organisme : CIHR
ID : 146586
Pays : Canada
Organisme : CIHR
ID : 142246
Pays : Canada
Organisme : CIHR
ID : 152863
Pays : Canada
Organisme : CIHR
ID : 152864
Pays : Canada
Organisme : CIHR
ID : 159567
Pays : Canada

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

Auteurs

Sujun Chen (S)

Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada; Ontario Institute for Cancer Research, Toronto, Ontario, Canada.

Vincent Huang (V)

Ontario Institute for Cancer Research, Toronto, Ontario, Canada.

Xin Xu (X)

Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.

Julie Livingstone (J)

Ontario Institute for Cancer Research, Toronto, Ontario, Canada.

Fraser Soares (F)

Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.

Jouhyun Jeon (J)

Ontario Institute for Cancer Research, Toronto, Ontario, Canada.

Yong Zeng (Y)

Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.

Junjie Tony Hua (JT)

Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.

Jessica Petricca (J)

Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.

Haiyang Guo (H)

Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.

Miranda Wang (M)

Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.

Fouad Yousif (F)

Ontario Institute for Cancer Research, Toronto, Ontario, Canada.

Yuzhe Zhang (Y)

Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada; College of Life Sciences, Central China Normal University, Wuhan, Hubei, China; College of Basic Medical Sciences, Dali University, Dali, Yunnan, China.

Nilgun Donmez (N)

Vancouver Prostate Centre, Vancouver, British Columbia, Canada.

Musaddeque Ahmed (M)

Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.

Stas Volik (S)

Vancouver Prostate Centre, Vancouver, British Columbia, Canada.

Anna Lapuk (A)

Vancouver Prostate Centre, Vancouver, British Columbia, Canada.

Melvin L K Chua (MLK)

Ontario Institute for Cancer Research, Toronto, Ontario, Canada.

Lawrence E Heisler (LE)

Ontario Institute for Cancer Research, Toronto, Ontario, Canada.

Adrien Foucal (A)

Ontario Institute for Cancer Research, Toronto, Ontario, Canada.

Natalie S Fox (NS)

Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Ontario Institute for Cancer Research, Toronto, Ontario, Canada.

Michael Fraser (M)

Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada; Ontario Institute for Cancer Research, Toronto, Ontario, Canada.

Vinayak Bhandari (V)

Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Ontario Institute for Cancer Research, Toronto, Ontario, Canada.

Yu-Jia Shiah (YJ)

Ontario Institute for Cancer Research, Toronto, Ontario, Canada.

Jiansheng Guan (J)

Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada; College of Electrical Engineering and Automation, Xiamen University of Technology, Xiamen, China.

Jixi Li (J)

State Key Laboratory of Genetic Engineering, Department of Neurology, School of Life Sciences and Huashan Hospital, Fudan University, Shanghai, China.

Michèle Orain (M)

Research Centre of CHU de Québec-Université Laval, Québec City, Québec, Canada.

Valérie Picard (V)

Research Centre of CHU de Québec-Université Laval, Québec City, Québec, Canada.

Hélène Hovington (H)

Research Centre of CHU de Québec-Université Laval, Québec City, Québec, Canada.

Alain Bergeron (A)

Research Centre of CHU de Québec-Université Laval, Québec City, Québec, Canada.

Louis Lacombe (L)

Research Centre of CHU de Québec-Université Laval, Québec City, Québec, Canada.

Yves Fradet (Y)

Research Centre of CHU de Québec-Université Laval, Québec City, Québec, Canada.

Bernard Têtu (B)

Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Stanley Liu (S)

Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada.

Felix Feng (F)

Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA; Department of Urology, University of California, San Francisco, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.

Xue Wu (X)

Translational Medicine Research Institute, Geneseeq Technology, Toronto, Ontario, Canada.

Yang W Shao (YW)

Translational Medicine Research Institute, Geneseeq Technology, Toronto, Ontario, Canada; School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.

Malgorzata A Komor (MA)

Translational Gastrointestinal Oncology, Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands; Oncoproteomics Laboratory, Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands.

Cenk Sahinalp (C)

Vancouver Prostate Centre, Vancouver, British Columbia, Canada.

Colin Collins (C)

Vancouver Prostate Centre, Vancouver, British Columbia, Canada; Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.

Youri Hoogstrate (Y)

Department of Urology, Erasmus Medical Centre, Rotterdam, the Netherlands.

Mark de Jong (M)

GenomeScan, Leiden, the Netherlands.

Remond J A Fijneman (RJA)

Translational Gastrointestinal Oncology, Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands.

Teng Fei (T)

College of Life and Health Sciences, Northeastern University, Shenyang, China.

Guido Jenster (G)

Department of Urology, Erasmus Medical Centre, Rotterdam, the Netherlands.

Theodorus van der Kwast (T)

Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.

Robert G Bristow (RG)

Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada; Division of Cancer Sciences, University of Manchester, Manchester, UK; The Christie NHS Foundation Trust, Manchester, UK; Manchester Cancer Research Centre, Manchester, UK.

Paul C Boutros (PC)

Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Ontario Institute for Cancer Research, Toronto, Ontario, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Centre, University of California, Los Angeles, Los Angeles, CA, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: pboutros@mednet.ucla.edu.

Housheng Hansen He (HH)

Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada. Electronic address: Hansenhe@uhnresearch.ca.

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Classifications MeSH

questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Widespread and Functional RNA Circularization...
questionsmedicales.fr › Phénomènes génétiques › Contexte génétique › Profil génétique › Widespread and Functional RNA Circularization...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › Widespread and Functional RNA Circularization...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Widespread and Functional RNA Circularization...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › microARN › Widespread and Functional RNA Circularization...
questionsmedicales.fr › Tissus › Glandes exocrines › Prostate › Widespread and Functional RNA Circularization...
questionsmedicales.fr › Maladies urogénitales › Tumeurs de l'appareil urogénital › Tumeurs de l'appareil génital mâle › Tumeurs de la prostate › Widespread and Functional RNA Circularization...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › Widespread and Functional RNA Circularization...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Maturation post-transcriptionnelle des ARN › Épissage des ARN › Widespread and Functional RNA Circularization...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN circulaire › Widespread and Functional RNA Circularization...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Widespread and Functional RNA Circularization...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ARN › Widespread and Functional RNA Circularization...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › Widespread and Functional RNA Circularization...