285 Differential DNA Methylation of microRNA-encoding Genes in Psoriatic Epidermis Highlights the Wnt Pathway

Psoriasis is an immune-mediated skin disease driven by the interplay between genetic predisposition and environmental factors. Epigenetic modifications have been reported in psoriasis, but methylation of miRNA-encoding genes (MIRs) has not previously explored. Using reduced representation bisulfite sequencing, we performed exhaustive genome-wide profiling MIR lesional, non-lesional healthy epidermis. We identified substantial differential MIRs (DM-MIRs), which 14 intersecting DM-MIRs clearly distinguished three phenotypes. Network analysis miRNA-target demonstrated striking enrichment Wnt signaling pathway, only inflammatory state also susceptibility. Mechanistically, that psoriasis-associated cytokines promoted increased certain MIRs, with a corresponding decrease RNA expression. Our findings add new level complexity to miRNA regulation psoriasis provide proof concept psoriatic micro-milieu may regulate transcription through methylation-dependent mechanism.