392 Next-generation Sequencing Identifies Epidermal Mirnas Deregulated in Psoriasis Skin

Psoriasis is a common chronic inflammatory skin disease, affecting 2-4% of world population. MicroRNAs (miRNAs) are short non-coding RNAs that regulate expression of the majority of protein-coding genes. In psoriasis, previous studies have identified deregulation in miRNA expression. Most of these studies utilized full-depth skin biopsies and thus may have missed the cell-specific miRNomic signature. Here, we analyzed the miRNome of CD45neg sorted epidermal cells from psoriasis patients and healthy skin by next-generation sequencing. We detected, differential expression of 104 miRNAs in the psoriatic epidermal cells, including several known and novel miRNAs. MiR-149 was identified as one of the significantly downregulated miRNAs, and qPCR analysis confirmed its downregulation in psoriatic lesional epidermal cells as compared to non-lesional or normal skin. In primary human keratinocytes and in 3D epidermal equivalents, miR-149 was significantly downregulated by IFN-γ. Overexpression of miR-149 suppressed the IFN--induced expression of IL-6 as well as T-cell attracting chemokines, while inhibition of endogenous miR-149 led to increased induction of these mediators. Taken together, we have characterized the cell-specific miRNome of epidermal non-immune cells in psoriasis skin and identified epidermal miRNAs, previously not associated with psoriasis. MiR-149 has been identified as a miRNA regulating the response of keratinocytes to IFN-γ. Our results can provide a basis for further functional studies of miRNAs in keratinocytes and lead to the identification of potential targets for topical therapy in psoriasis.