Journal
CELL
Volume 176, Issue 4, Pages 831-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2019.01.025
Keywords
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Funding
- Princess Margaret Cancer Foundation
- Canada Foundation for Innovation and Ontario Research Fund [CFI32372]
- NSERC discovery grant [498706]
- Canadian Cancer Society innovation grants [705649, 703800]
- Prostate Cancer Canada [RS2014-01, RS2016-1022]
- CIHR [146586, 142246, 152863, 152864, 159567]
- Ontario Institute for Cancer Research
- CIHR New Investigator Awards
- Princess Margaret Cancer Foundation [886012001223]
- OMIR Early Researcher Award
- Shanghai Committee of Science and Technology [18430711400]
- CIHR Fellowship
- Faculty of Medicine Award
- University of Toronto Fellowship
- STARS21 Training program fellowship
- CTMM (the Netherlands) NGS ProToCol [03O-402]
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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.
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