Abstract
Psoriasis is a common, chronic, and relapsing skin disease characterized by hyperproliferation of keratinocytes and apoptosis delay. However, the molecular mechanisms underlying the progression of psoriasis remain elusive. MicroRNAs (miRNAs) are single-stranded, small non-coding RNAs that play a crucial role in the development of psoriasis by promoting targeted mRNA degradation or translational inhibition. Here, we report that miR-214-3p, one of the downregulated miRNAs identified in the skin of psoriatic patients and imiquimod (IMQ)-induced mouse models, can negatively regulate the expression of forkhead box M1 (FOXM1). miR-214-3p inhibition leads to hyperproliferation and increased apoptosis of keratinocytes in vitro. Moreover, we show that miR-214-3p inhibition causes an arrest of the cell cycle at the S stage by elevating the expression of NEK2, KIF20A, CENP-A, CENP-F, and Cyclin B1 and by reducing the expression of Cyclin D1 in HaCaT cells. In vivo, the administration of miR-214-3p attenuates the psoriasis-like phenotype in IMQ-induced mice. Collectively, our results suggest that miR-214-3p/FOXM1 axis in keratinocytes could be a novel target in the treatment of psoriasis.
Highlights
Psoriasis is a chronic autoimmune skin disease that varies greatly from person to person
Of the differentially expressed miRNAs analyzed, we focused on miR-214-3p, which was remarkably downregulated in psoriatic tissue and significantly up-regulated in psoriatic skin after treatment with adalimumab [14] (Figure 1A)
Previous studies suggested that the imiquimod (IMQ)-induced psoriasis mouse model could closely recapitulate the phenotype in psoriasis patients [25]
Summary
Psoriasis is a chronic autoimmune skin disease that varies greatly from person to person. Anti-miR-31 administration could markedly decrease keratinocyte hyperproliferation and dermal cellular infiltration [11] Another case is miR-197, which has a pronounced decrease in psoriatic lesions. Activation of the expression of miR-197 could inhibit keratinocytes proliferation and migration [12] These studies strongly suggest that the inhibition of upregulated miRNAs or the supplementation of mimics of downregulated miRNAs in psoriatic skin lesions would offer benefits in the treatment of topical psoriasis. The expression of miR-214-3p was increased by 1.73-fold in the psoriatic patient lesional skin after treated with adalimumab for 14 days [14]. These data suggest that miR-214-3P may play an important role in the progression of psoriasis. A systematic understanding of how miR-214-3p contributes to psoriasis is still lacking
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