Circular RNA expression is abundant and correlated to aggressiveness in early-stage bladder cancer

Trine Line Hauge Okholm; Morten Muhlig Nielsen; Mark Hamilton; Lise-Lotte Christensen; Søren Vang; Jakob Hedegaard; Thomas Birkballe Hansen; Jørgen Kjems; Lars Dyrskjøt; Jakob Skou Pedersen

doi:10.1038/s41525-017-0038-z

Circular RNA expression is abundant and correlated to aggressiveness in early-stage bladder cancer

Trine Line Hauge Okholm, Morten Muhlig Nielsen, Mark Hamilton, Lise-Lotte Christensen, Søren Vang, Jakob Hedegaard, Thomas Birkballe Hansen, Jørgen Kjems, Lars Dyrskjøt, Jakob Skou Pedersen

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

93 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Artikelnummer	36
Tidsskrift	npj Genomic Medicine
Vol/bind	2
Nummer	1
DOI	https://doi.org/10.1038/s41525-017-0038-z
Status	Udgivet - 1 dec. 2017

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title = "Circular RNA expression is abundant and correlated to aggressiveness in early-stage bladder cancer",

abstract = "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.",

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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 - 2017/12/1

Y1 - 2017/12/1

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.

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Circular RNA expression is abundant and correlated to aggressiveness in early-stage bladder cancer

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