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O'Leary, V.B. ; Smida, J. ; Matjanovski, M. ; Brockhaus, C. ; Winkler, K. ; Mörtl, S. ; Ovsepian, S.V. ; Atkinson, M.J.

The circRNA interactome-innovative hallmarks of the intra- and extracellular radiation response.

Oncotarget 8, 78397-78409 (2017)
Publ. Version/Full Text Research data DOI PMC
Generated by Quaking (QKI), circular RNAs (circRNAs) are newly recognised non-coding RNA (ncRNA) members characterised by tissue specificity, increased stability and enrichment within exosomes. Studies have shown that ionizing radiation (IR) can influence ncRNA transcription. However, it is unknown whether circRNAs or indeed QKI are regulated by IR. Microarray circRNA profiling and next generation sequencing revealed that circRNA expression was altered by low and medium dose exposure sourced predominantly from genes influencing the p53 pathway. CircRNAs KIRKOS-71 and KIRKOS-73 transcribed from the WWOX (WW Domain Containing Oxidoreductase) tumor suppressor (a p53 regulator) responded within hours to IR. KIRKOS-71 and KIRKOS-73 were present in exosomes yet exhibited differential transcript clearance between irradiated cell lines. Dual-quasar labelled probes and in-situ hybridization demonstrated the intercellular distribution of KIRKOS-71 and KIRKOS-73 predominantly within the perinucleus. QKI knockdown removed nuclear expression of these circRNAs with no significant effect on cytosolic KIRKOS-71 and KIRKOS-73. Distinct QKI transcription between cell lines and its augmented interaction with KIRKOS-71 and KIRKOS-73 was noted post IR. This foremost study provides evidence that QKI and circRNAs partake in the cellular irradiation response. KIRKOS-71 and KIRKOS-73 as stable secreted circRNAs may afford vital characteristics worth syphoning as promising diagnostic radiotherapy biomarkers.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Kirkos ; Quaking ; Wwox ; Circrna ; Exosomes; Circular Rnas; P53; Expression; Microrna; Cancer; Identification; Biogenesis; Proteins; Insights; Cells
ISSN (print) / ISBN 1949-2553
e-ISSN 1949-2553
Journal OncoTarget
Quellenangaben Volume: 8, Issue: 45, Pages: 78397-78409 Article Number: , Supplement: ,
Publisher Impact Journals LLC
Publishing Place Orchard Park
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Radiation Biology (ISB)
Institute of Biological and Medical Imaging (IBMI)