Background: Psoriasis 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. Results:Using 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. Conclusions:We 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, 3 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. BackgroundPsoriasis is one of the most common chronic inflammatory skin conditions, with 1-3% of the adult population affected worldwide [1]. It is defined by a pronounced hyperproliferation and deficient terminal differentiation of the keratinocytes. Moreover, a complex interplay between different cell types (e.g. T cells and dendritic cells) and a variety of cytokines are known to contribute in the development of psoriasis. The pathogenesis is also based on a complex synergy between genetic predisposition, major histocompatibility alleles, and a variety of environmental triggers [2]. From the molecular point of view, however, the mechanisms responsible for the interactions between keratinocytes and inflammatory cells infiltrating the epidermis are still not fully understood. The analysis of the molecular backdrop of psoriasis has described numerous disease-associated genes and proteins with abnormal expression patterns [3], but little is...

Psoriasis is a common chronic inflammatory skin disease accompanied by heterogenous clinical and histological features, including a characteristic keratinocyte hyperproliferation and dermal immunogenic profile. In addition, psoriasis is associated with widespread transcriptomic alterations including changes in microRNA (miRNA) and circular RNA (circRNA) abundance, which constitute non-coding RNA (ncRNA) classes with specific regulatory capacities in diverse physiological and pathological processes. However, the knowledge about the expression dynamics of ncRNA during psoriasis treatment is sparse. To elucidate the dynamics of miRNA and circRNA abundance during secukinumab (anti-IL-17A) treatment, we studied their expression patterns in skin biopsies from 14 patients with severe plaque-type psoriasis before and during an 84-day secukinumab therapy at day 0, 4, 14, 42, and 84 using NanoString nCounter technology. We found a comprehensive downregulation of the majority of investigated circRNAs and specific alterations in the miRNA profile, including an upregulation of miR-203a-3p, miR-93-5p, and miR-378i in lesional compared to non-lesional skin before treatment. During treatment, the circRNAs progressively returned to the expression levels observed in non-lesional skin and already four days after treatment initiation most circRNAs were significantly upregulated. In comparison, for miRNAs, the normalization to baseline during treatment was delayed and limited to a subset of miRNAs. Moreover, we observed a strong correlation between multiple circRNAs, including ciRS-7 and circPTPRA, and the psoriasis area and severity index (PASI). Similar pronounced correlations could, however, not be found for miRNAs. Finally, we did not observe any significant changes in circRNA expression in peripheral blood mononuclear cells during treatment. In conclusion, we uncovered a rapid shift in global circRNA abundance upon anti-IL-17A treatment, which predated clinical and histological improvements, and a strong correlation with PASI, indicating a biomarker potential of individual circRNAs.

Cutaneous Squamous Cell Carcinoma (cSCC) is the most common and fastest-increasing cancer with metastatic potential. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are novel regulators of gene expression and little is known about their altered expression in cSCC. To elucidate cSCC associated coding and non-coding transcriptomic changes, we performed RNA-seq of 9 cSCCs and 7 healthy skin samples. Differential expression analysis was performed by edgeR. CircRNAs were identified using the find_circ and CIRCexplorer pipelines. Altered expression of 5,352 protein-coding genes, 908 lncRNAs and 55 circular RNAs was identified. Targets of 519 transcription factors were enriched among DEGs, 105 of which displayed altered level in cSCCs, including fundamental regulators of skin development and cSCC malignancy (MYC, RELA, ETS1, TP63). Pathways related to cell cycle, apoptosis, inflammation and epidermal differentiation were enriched. In addition to known oncogenic lncRNAs (PVT1, LUCAT1, CASC9), a set of skin-specific lncRNAs were also dysregulated. A global downregulation of circRNAs was observed in cSCC, and novel circRNAs, including skin-enriched circ_IFFO2 and circ_POF1B, were identified. Results from the RNA-seq were further validated in an expanded cohort using NanoString nCounter assays. In conclusion, through deep sequencing approach we have identified a reference set of coding and non-coding transcripts with altered expression in cSCC, which represent potential therapeutic targets or biomarkers.