Psoriasis is a common, chronically relapsing inflammatory skin disease characterized by epidermal hyperproliferation. LncRNAs are >200 nucleotide long transcripts, which do not code for protein but possess diverse regulatory functions. To date, little is known about the contribution of lncRNAs to psoriasis. Here, we identified lncRNAs with altered expression using transcriptomic profiling on epidermal cells sorted from psoriasis and healthy skin. LINC00958 was identified as a lncRNA overexpressed in keratinocytes from psoriasis skin lesions, and confirmed by RT-qPCR and single molecule in situ hybridization. Using confocal microscopy and analysis of subcellular fractions, we demonstrated that LINC00958 is mainly localized in the cytoplasm of keratinocytes. LINC00958 expression was induced by IL-17A in primary keratinocytes through C/EBP-β and the p38 signaling pathway. Transcriptomic analysis of LINC00958-depleted keratinocytes revealed changes in the expression of a large number of genes associated with proliferation and cell cycle. In line with this, inhibition of LINC00958 in keratinocytes led to decreased proliferation as judged by Ki67 expression, IncuCyte imaging, and EdU incorporation assay. Moreover, using a phospho-kinase array we showed that LINC00958-depletion led to decreased p38 phosphorylation in keratinocytes. Immunoblotting showed that inhibition of LINC00958 suppressed not only basal but also IL-17A-induced phosphorylation of p38 in primary human keratinocytes. In summary, our data suggest that the IL-17A-induced LINC00958 can contribute to the pathological circuits in psoriasis by reinforcing IL-17A-induced epidermal hyperproliferation.

ESDR318 - The long non-coding RNA LINC00958 is overexpressed in psoriasis epidermis and induces keratinocyte proliferation

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.