Abstract
Background: Atopic 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. Objectives: To 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. Methods: We 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. Results: We 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. Conclusion: Psoriasis 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.
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