The Long Noncoding RNA LINC00958 Is Induced in Psoriasis Epidermis and Modulates Epidermal Proliferation

Psoriasis is a common, immune-mediated skin disease characterized by epidermal hyperproliferation and chronic skin inflammation. Long noncoding RNAs are >200 nucleotide-long transcripts that possess important regulatory functions. To date, little is known about the contribution of long noncoding RNAs to psoriasis. In this study, we identify LINC00958 as a long noncoding RNA overexpressed in keratinocytes (KCs) from psoriasis skin lesions, in a transcriptomic screen performed on KCs sorted from psoriasis and healthy skin. Increased levels of LINC00958 in psoriasis KCs were confirmed by RT-qPCR and single-molecule in situ hybridization. Confocal microscopy and analysis of subcellular fractions showed that LINC00958 is mainly localized in the cytoplasm of KCs. IL-17A, a key psoriasis cytokine, induced LINC00958 in KCs through C/EBP-b and the p38 pathway. The inhibition of LINC00958 led to decreased proliferation as measured by Ki-67 expression, live cell analysis imaging, and 5-ethynyl-2-deoxyuridine assays. Transcriptomic analysis of LINC00958-depleted KCs revealed enrichment of proliferation-and cell cycle-related genes among differentially expressed transcripts. Moreover, LINC00958 depletion led to decreased basal and IL-17A-induced phosphorylation of p38. Further-more, IL-17A-induced KC proliferation was counteracted by the inhibition of LINC00958. In summary, our data support a role for the IL-17A-induced long noncoding RNA, LINC00958, in the pathological circuits of psoriasis by reinforcing IL-17A-induced epidermal hyperproliferation.

Automated summary

This study identified LINC00958 as an overexpressed long noncoding RNA in keratinocytes from psoriasis skin lesions. IL-17A induced LINC00958 expression in keratinocytes through C/EBP-b and the p38 pathway. Inhibiting LINC00958 led to decreased cell proliferation and altered expression of cell cycle-related genes in keratinocytes.