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    Widespread and functional RNA circularization in localized prostate cancer

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    Authors
    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
    Tetu, 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, Robert G
    Boutros, PC
    He, HH
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    Affiliation
    Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada;
    Issue Date
    2019
    
    Metadata
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    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.
    Citation
    Chen S, Huang V, Xu X, Livingstone J, Soares F, Jeon J, et al. Widespread and functional RNA circularization in localized prostate cancer. Cell. 2019 Feb 7;176(4):831-43 e22.
    Journal
    Cell
    URI
    http://hdl.handle.net/10541/621643
    DOI
    10.1016/j.cell.2019.01.025
    PubMed ID
    30735634
    Additional Links
    https://dx.doi.org/10.1016/j.cell.2019.01.025
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.cell.2019.01.025
    Scopus Count
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