High-throughput RNA sequencing from paired lesional- and non-lesional skin reveals major alterations in the psoriasis circRNAome

Abstract

BackgroundPsoriasis is a chronic inflammatory skin disease characterized by hyperproliferation and abnormal differentiation of keratinocytes. It is one of the most prevalent chronic inflammatory skin condition in adults worldwide, with a considerable negative impact on quality of life. Circular RNAs (circRNAs) are a recently identified type of non-coding RNA with diverse cellular functions related to their exceptional stability. In particular, some circRNAs can bind and regulate microRNAs (miRNAs), a group of RNAs that play a role in the pathogenesis of psoriasis. The aim of this study was to characterize the circRNAome in psoriasis and to assess potential correlations to miRNA expression patterns.\n\nResultsUsing high-throughput RNA-sequencing (RNA-seq) and NanoString nCounter technology, we found a substantial down-regulation of circRNA expression in lesional skin compared to non-lesional skin from psoriasis patients. We saw that this mainly applies to the epidermis by analyzing laser capture microdissected tissues and by RNA chromogenic in situ hybridization (CISH). We also found that the majority of the circRNAs were downregulated independent of their corresponding linear host genes. The observed downregulation of circRNAs in psoriasis was not due to altered expression levels of factors known to affect circRNA biogenesis, nor because lesional skin contained an increased number of inflammatory cells such as lymphocytes. Finally, we saw that the overall differences in available miRNA binding sites on the circRNAs between lesional and non-lesional skin did not correlate with differences in miRNA expression patterns.\n\nConclusionsWe have performed the first genome-wide circRNA profiling of paired lesional and non-lesional skin from psoriasis patients and revealed that circRNAs are much less abundant in the lesional samples. Whether this is a cause or a consequence of the disease remains to be revealed, however, we found no evidence that the loss of miRNA binding sites on the circRNAs could explain differences in miRNA expression reported between lesional and non-lesional skin.