375 miR-484: a microRNA with altered subcellular localization in psoriasis keratinocytes

Psoriasis is a common chronic inflammatory skin disease characterized by a vicious circle of inflammation in the skin as a result of aberrant keratinocyte-immune cell communication. microRNAs (miRNAs) are short non-protein coding RNAs that can repress up to hundreds of target genes. We and others have previously shown the involvement of miRNAs in the pathogenesis of psoriasis. Recently we identified miRNAs differentially expressed in psoriasis keratinocytes, by small RNA sequencing of CD45neg epidermal cells from psoriasis lesional and non-lesional skin and healthy skin. MiRNA-484 was upregulated in keratinocytes of psoriatic lesions compared to those in non-lesional and healthy skin. Here, we aimed to investigate the regulation and function of miR-484 in keratinocytes. Interferon-γ (IFN-g) was identified as an inducer of miR-484 in cultured keratinocytes through JAK/STAT- and C/EBP-β signaling. Using in situ hybridisation on psoriasis and healthy skin sections, we confirmed the upregulation of miR-484 in psoriasis epidermis. Surprisingly, the subcellular localization of miR-484 showed predominantly nuclear localization in healthy epidermis, while mainly cytoplasmic localization was observed in psoriasis epidermis. Of note, miRNAs exert their function in the cytoplasm by binding to their target mRNAs, and alterations in the subcellular localization can therefore affect their functions. In sum, miR-484 was identified as a miRNA induced in psoriasis keratinocytes by IFN-g, and its subcellular localization is altered in psoriasis epidermis. Further studies will be needed to explore its molecular targets and function in healthy and psoriasis epidermis.