GSE123940
RNA-seq after KD or OE of circRNAs or linear gene
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 tumours 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 tumour 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 for cell proliferation. 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 the linear and circular transcriptome. Overall design: RNA-seq was performed aftercircGOLPH3 and circSTAU2 KD and OE and siCSNK1G3