Multi-Omics analysis identified DNA methylation and miRNAs mediated gene regulatory networks in Psoriasis

Abstract Psoriasis is a complex, autoimmune skin disease characterized by a reversible albeit relapsing predisposition in the skin of a patient. Insights into the regulatory mechanisms at the transcriptional and post-transcriptional levels are instrumental into further understanding of the multi-factorial gene regulation of the disease etiology and pathogenesis. In our study, we have carried out multi-omics integrative analysis of total RNA-sequencing, small RNA-sequencing and DNA methylation profiling from the psoriatic and adjacent normal skin tissues. Our multi-omics analysis have identified the genes and biological processes regulated by DNA methylation and microRNAs either independently or in combination. Gene enrichment networks and pathway analysis demonstrated that miRNAs are the sole mediators in cell cycle progression and checkpoint signaling, regulating keratinocyte hyper-proliferation, one of the prominent factor for skin phenotype observed in psoriatic tissues. DNA methylation contrarily was more predominant in regulation of immune and inflammatory responses, another causative factor in psoriasis pathogenesis. Several key processes implicated in disease pathogenesis were governed by combination of both regulatory mechanisms including Th17 cell differentiation and JAK-STAT signaling. The reversible nature of DNA methylation and miRNA-mediated regulation of gene expression illustrate the importance of our findings from multi-omics analysis to understand a complex disease with reversible phenotype.