200 Genome-wide analysis of long non-coding RNA expression profiles in keratinocytes from psoriasis skin

Abstract

Psoriasis is a common, chronically relapsing inflammatory skin disease, affecting the patients’ life quality substantially. Psoriasis has a strong genetic background and a large number of genetic susceptibility loci have been identified. In psoriatic plaques, keratinocytes, the major cell type in the epidermis, undergo hyperproliferation and aberrant differentiation. The regulation of these processes in keratinocytes is not fully understood. Long non-coding RNAs are >200 nucleotide long transcripts, which do not code for protein but regulate other genes. Little is known about their involvement in epidermal alterations in psoriasis. In this study, we aimed to explore the potential contribution of long non-coding RNAs to epidermal alterations in psoriasis. In order to detect changes in the non- coding epidermal transcriptome, keratinocytes were sorted from skin biopsies collected from healthy skin of volunteers as well as from non-lesional and lesional skin of patients with psoriasis. Affymetrix Human Transcriptome Array 2.0 platform was used to identify differentially expressed lncRNAs. Microarray analysis identified 43 lncRNAs that were significantly up-regulated and 37 lncRNAs that were down-regulated in keratinocytes from psoriasis lesional skin as compared to healthy skin. 65 lncRNAs were deregulated in the lesional skin when compared with non-lesional skin. Analysis of overlap between the genomic loci coding for lncRNAs and known psoriasis susceptibility regions identified several lncRNAs, which are localized in genomic regions in the vicinity of known psoriasis susceptibility loci. We identified the LINC00958 as a lncRNA to be overexpressed in keratinocytes from psoriasis lesional skin, as compared with non-lesional and healthy skin. We have confirmed its overexpression in keratinocytes of psoriasis skin by qPCR and RNAscope in situ hybridization. Our results suggest that lncRNAs may contribute to epidermal dysfunction in psoriatic skin and that lncRNA modulation may be a novel treatment option for psoriasis in the future.