Elevated SNHG15 empowers keratinocytes hyperproliferation through activation of STAT3/Cyclin D1 axis in psoriasis.

Psoriasis is a common inflammatory skin disease with characterization of epidermal hyperplasia and sustained skin inflammation. Long noncoding RNAs (lncRNAs), which contain more than 200 nucleotide-long transcripts, are emerging as the crux of epigenetic regulators in multiple biological processes and diseases. However, how lncRNAs contribute to the etiology of psoriasis remains to be elucidated. For the first time, this study revealed that SNHG15, which was elevated in cytokines-stimulated keratinocytes and psoriasis lesions, promoted keratinocytes hyperproliferation. Mechanistically, SNHG15 fueled epithelial pathology through activation of STAT3/Cyclin D1 axis. Intriguingly, activation of STAT3 enhanced SNHG15 transcription to form a positive feed-back modulatory loop and consequently augmented the skin lesions in psoriasis. Furthermore, knock down the expression of SNHG15 can counteract the IMQ-induced keratinocytes hyperproliferation in vivo. Taken together, our findings uncover that SNHG15 facilitates epidermal hyperplasia via STAT3/Cyclin D1 axis, which might provide a novel therapeutic avenue for psoriasis treatment.