Cited by 591Circular RNAs in diseasesRNA Research and SplicingCancer-related molecular mechanisms research

Widespread and Functional RNA Circularization in Localized Prostate Cancer

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Chen, Sujun, Huang, Vincent, Xu, Xin, Livingstone, Julie, Soares, Fraser, Jeon, Jouhyun, Zeng, Yong, Hua, Junjie Tony +41 more·2019·Cell

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.

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Crossref · 10.1016/j.cell.2019.01.025

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Authors
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., Foucal, A., Fox, N. S., Fraser, M., Bhandari, V., Shiah, Y.-J., 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, Y. W., Komor, M. A., Sahinalp, C., Collins, C., Hoogstrate, Y., de Jong, M., Fijneman, R. J. A., Fei, T., Jenster, G., van der Kwast, T., Bristow, R. G., Boutros, P. C., & He, H. H.
Affiliations
  • Ontario Institute for Cancer Research (CA)
  • University Health Network (CA)
  • Vancouver Prostate Centre (CA)
  • Fudan University (CN)
  • Centre de recherche du CHU de Québec-Université Laval (CA)
  • Sunnybrook Health Science Centre (CA)
  • University of California, San Francisco (US)
  • Nanjing Medical University (CN)
  • The Netherlands Cancer Institute (NL)
  • University of British Columbia (CA)
  • Erasmus MC (NL)
  • Northeastern University (CN)
Corresponding author
  • Boutros, Paul C.
  • He, Housheng Hansen
Venue
Cell
Publisher
Elsevier BV
Published
2019-02
Volume
176
Issue
4
Pages
831-843.e22
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2913336364
Cited by
544
References
91
Citations by year
2026: 13 · 2025: 26 · 2024: 107 · 2023: 44 · 2022: 105 · 2021: 110 · 2020: 83 · 2019: 55
FWCI
31.45
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
Funders
  • Princess Margaret Cancer Foundation (886012001223)
  • Canada Foundation for Innovation and Ontario Research Fund (CFI32372)
  • NSERC (498706)
  • Canadian Cancer Society (705649, 703800)
  • Prostate Cancer Canada (RS2014-01, RS2016-1022)
  • CIHR (146586, 142246, 152863, 152864, 159567)
  • Ontario Institute for Cancer Research
  • TFRI
  • OMIR
  • Shanghai Committee of Science and Technology (18430711400)
  • University of Toronto
  • STARS21
  • CTMM (03O-402)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
circular RNA, RNA circularization, localized prostate cancer, back-splicing, intraductal carcinoma, metastatic prostate cancer, miR-181, cell proliferation, transcriptomic subtypes
MeSH terms
Genetic Profile, RNA, Circular, Humans, Male, Prostate, Prostatic Neoplasms, RNA, RNA Splicing, Sequence Analysis, RNA, Gene Expression Profiling, RNA, Untranslated, MicroRNAs, HEK293 Cells, Transcriptome

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