Characterization of Circular RNA Transcriptomes in Psoriasis and Atopic Dermatitis Reveals Disease-specific Expression Profiles

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  • Liviu I Moldovan
  • Lam C Tsoi, University of Michigan Medical School
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  • Uppala Ranjitha, University of Michigan Medical School
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  • Henrik Hager, Department of Dermatology, Venereology and Allergy, University Clinics of Schleswig-Holstein, Kiel, Germany., University Hospital Schleswig-Holstein, Department of Gynaecology and Obstetrics, University Hospital of Schleswig-Holstein, Christian-Albrechts University Kiel, Campus Kiel, 24105, Kiel, Germany., Zoological Institute, University of Kiel, Kiel, Germany., Medizinische Hochschule, Hanover, Germany; Private Practice Lübeck, Germany
  • ,
  • Stephen Weidinger, Hospital Lillebaelt, Middelfart, Denmark, University of Southern Denmark, Odense, Denmark, and Aarhus University Hospital, Aarhus, Denmark.
  • ,
  • Johann E Gudjonsson, University of Michigan Medical School
  • ,
  • Jørgen Kjems
  • Lasse S Kristensen

Atopic dermatitis (AD) and psoriasis, two common chronic inflammatory skin diseases that are associated with various comorbidities. Circular RNA (circRNA) constitute a major class of non-coding RNAs that have been implicated in many human diseases, although their potential involvement in inflammatory skin diseases remains elusive. Here, we compare and contrast the circRNA expression landscapes in paired lesional and non-lesional skin from psoriasis and AD patients relative to skin from unaffected individuals using high-depth RNA-seq data. CircRNAs and their cognate linear transcripts were quantified using the circRNA detection algorithm, CIRI2, and in situ hybridization and Sanger sequencing was used for validation purposes. We identified 39,286 circRNAs among all samples and found that psoriasis and AD lesional skin could be distinguished from non-lesional and healthy skin based on circRNA expression landscapes. In general, circRNAs were less abundant in lesional relative to non-lesional and healthy skin. Differential expression analyses revealed many significantly downregulated circRNAs, mainly in psoriasis lesional skin, and a strong correlation between psoriasis and AD-related circRNA expression changes was observed. Two individual circRNAs, ciRS-7 (also known as CDR1as) and circZRANB1, was specifically dysregulated in psoriasis and show promise as biomarkers for discriminating AD from psoriasis. In conclusion, the circRNA transcriptomes of psoriasis and AD share expression features, including a global downregulation relative to healthy skin, but this is most pronounced in psoriasis, and only psoriasis is characterized by several circRNAs being dysregulated independently of their cognate linear transcripts. Finally, specific circRNAs could potentially be used to distinguish AD from psoriasis.

Original languageEnglish
JournalExperimental Dermatology
Publication statusE-pub ahead of print - 28 Oct 2020

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