open access publication

Article, 2017

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

npj Genomic Medicine, ISSN 2056-7944, Volume 2, 1, Page 36, 10.1038/s41525-017-0038-z

Contributors

Okholm, Trine Line Hauge 0000-0002-2779-4029 (Corresponding author) [1] Nielsen, Morten Muhlig 0000-0002-8972-7577 [1] Hamilton, Mark Patrick [2] Christensen, Lise Lotte [1] Vang, Søren 0000-0002-1899-4205 [1] Hedegaard, Jakob [1] Hansen, Thomas Birkballe 0000-0002-7573-9657 [3] Kjems, Jo Rgen K 0000-0003-4128-9317 [3] Dyrskjøt, Lars 0000-0001-7061-9851 [1] Pedersen, Jakob Skou 0000-0002-7236-4001 (Corresponding author) [1] [3]

Affiliations

  1. [1] Aarhus University Hospital
    2. [NORA names: Central Denmark Region; Hospital; Denmark; Europe, EU; Nordic; OECD];
  2. [2] Baylor College of Medicine
    3. [NORA names: United States; America, North; OECD];
  3. [3] Aarhus University
    4. [NORA names: AU Aarhus University; University; Denmark; Europe, EU; Nordic; OECD]

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.

Keywords

Alu repeats, RNA, RNA expression, abundant circRNAs, aggression, analysis, analysis of progression-free survival, biological features, biomarker potential, biomarkers, bladder cancer, cancer, cancer types, circCDYL, circHIPK3, circRNAs, circular RNA expression, circular RNAs, constraint elements, correlated to aggressiveness, early-stage bladder cancer, elements, evidence, exon, expressed circRNAs, expression, expression of circRNAs, features, field, field of study, function, genes, host, host genes, linear transcripts, microRNA target sites, non-muscle-invasive bladder cancer, patients, potential of circular RNAs, prognostic biomarker, progression, progression-free survival, repeats, results, sites, study, subtypes, survival, target site, transcription, tumor, tumor subtypes, tumorigenesis, type

Funders

  • Lundbeck Foundation
  • Danish Cancer Society
  • Novo Nordisk Foundation

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