TY - JOUR
T1 - Circular RNA expression is abundant and correlated to aggressiveness in early-stage bladder cancer
AU - Okholm, Trine Line Hauge
AU - Nielsen, Morten Muhlig
AU - Hamilton, Mark
AU - Christensen, Lise-Lotte
AU - Vang, Søren
AU - Hedegaard, Jakob
AU - Hansen, Thomas Birkballe
AU - Kjems, Jørgen
AU - Dyrskjøt, Lars
AU - Pedersen, Jakob Skou
PY - 2017/11/28
Y1 - 2017/11/28
N2 - The functions and biomarker potential of circular RNAs (circRNAs) in various cancer types are a rising field of study, as emerging evidence relates circRNAs to tumorigenesis. Here, we profiled the expression of circRNAs in 457 tumors from patients with non-muscle-invasive bladder cancer (NMIBC). We show that a set of highly expressed circRNAs have conserved core splice sites, are associated with Alu repeats, and enriched with Synonymous Constraint Elements as well as microRNA target sites. We identified 113 abundant circRNAs that are differentially expressed between high and low-risk tumor subtypes. Analysis of progression-free survival revealed 13 circRNAs, among them circHIPK3 and circCDYL, where expression correlated with progression independently of the linear transcript and the host gene. In summary, our results demonstrate that abundant circRNAs possess multiple biological features, distinguishing them from low-expressed circRNAs and non-circularized exons, and suggest that circRNAs might serve as a new class of prognostic biomarkers in NMIBC.
AB - The functions and biomarker potential of circular RNAs (circRNAs) in various cancer types are a rising field of study, as emerging evidence relates circRNAs to tumorigenesis. Here, we profiled the expression of circRNAs in 457 tumors from patients with non-muscle-invasive bladder cancer (NMIBC). We show that a set of highly expressed circRNAs have conserved core splice sites, are associated with Alu repeats, and enriched with Synonymous Constraint Elements as well as microRNA target sites. We identified 113 abundant circRNAs that are differentially expressed between high and low-risk tumor subtypes. Analysis of progression-free survival revealed 13 circRNAs, among them circHIPK3 and circCDYL, where expression correlated with progression independently of the linear transcript and the host gene. In summary, our results demonstrate that abundant circRNAs possess multiple biological features, distinguishing them from low-expressed circRNAs and non-circularized exons, and suggest that circRNAs might serve as a new class of prognostic biomarkers in NMIBC.
UR - http://www.scopus.com/inward/record.url?scp=85041342894&partnerID=8YFLogxK
U2 - 10.1038/s41525-017-0038-z
DO - 10.1038/s41525-017-0038-z
M3 - Journal article
C2 - 29263845
VL - 2
JO - npj Genomic Medicine
JF - npj Genomic Medicine
IS - 1
M1 - 36
ER -