MicroRNAs (
miRNAs) are small non-coding RNAs that have emerged as central regulators of gene expression and powerful
biomarkers of disease. Much is yet unknown about their role in
psoriasis pathology. To globally characterize the miRNAome of psoriatic skin, skin biopsies were collected from psoriatic cases (n = 75) and non-psoriatic controls (n = 46) and
RNA sequenced. Count data were meta-analysed with a previously published dataset (cases, n = 24, controls, n = 20), increasing the number of psoriatic cases fourfold from previously published studies. Differential gene expression analyses were performed comparing lesional psoriatic (PP), non-lesional psoriatic (PN) and control (NN) skin. Further, functional enrichment and cell-specific analyses were performed. Across all contrasts, we identified 439 significantly differentially expressed
miRNAs (DEMs), of which 85 were novel for
psoriasis and 11 were related to disease severity. Meta-analyses identified 20 DEMs between PN and NN, suggesting an inherent change in the constitution of all skin in
psoriasis. By integrating the
miRNA transcriptome with
mRNA target interactions, we identified several functionally enriched terms, including "
thyroid hormone signalling," "
insulin resistance" and various
infectious diseases. Cell-specific expression analyses revealed that the upregulated DEMs were enriched in epithelial and immune cells. This study provides the most comprehensive overview of the miRNAome in psoriatic skin to date and identifies a
miRNA signature related to
psoriasis severity. Our results may represent molecular links between
psoriasis and related comorbidities and have outlined potential directions for future functional studies to identify
biomarkers and treatment targets.