Characterization of Circular RNA Transcriptomes in Psoriasis and Atopic Dermatitis Reveals Disease-specific Expression Profiles
AbstractBackgroundAtopic dermatitis (AD) and psoriasis, two chronic inflammatory skin diseases, affect a large number of individuals worldwide, and 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.ObjectivesTo 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. Moreover, to correlate circRNA expression to disease severity.MethodsWe analyzed high-depth RNA-seq data from paired lesional and non-lesional skin samples from 27 AD patients, 28 psoriasis patients, and 38 healthy controls. CircRNAs and their cognate linear transcripts were quantified using the circRNA detection algorithm, CIRI2.ResultsWe identified 39,286 unique circRNAs in total 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. A subset of circRNAs, including ciRS-7, was specifically dysregulated in psoriasis and show promise as biomarkers for discriminating AD from psoriasis.ConclusionPsoriasis and circRNA transcriptomes share expression features, including a global downregulation, but only psoriasis is characterized by several circRNAs being dysregulated independently of their cognate linear transcripts.