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Αλέξανδρος Γ. Σφακιανάκης

Sunday, July 11, 2021

MicroRNA‐215‐5p inhibits the proliferation of keratinocytes and alleviates psoriasis‐like inflammation by negatively regulating DYRK1A and its downstream signalling pathways

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Abstract

Psoriasis is a chronic inflammatory disease characterized by abnormal hyperproliferation and differentiation. The object of this study is to explore the role of microRNA-215-5p in psoriasis-like inflammation. The expression of miR-215-5p was found to be down-regulated in pro-inflammatory factor-stimulated HaCaT cells and imiquimod (IMQ)-treated skin tissues. Overexpression of miR-215-5p suppressed the proliferation and cell cycle progression of HaCaT cells. Further, miR-215-5p agomir alleviated the disease severity, pathological features and Ki67 positive cells in IMQ-treated mice. Luciferase assay confirmed that miR-215-5p could bind to the 3′UTR of DYRK1A. The in vitro and in vivo results showed that miR-215-5p negatively regulates DYRK1A, which further inhibited EGFR and its downstream signalling pathways, AKT and ERK. Collectively, our results provide evidence that overexpression of miR-215-5p inhibits the proliferation of HaCaT cells and alleviates psoriasis-like inflammati on partly by DYRK1A mediated inhibition of the EGFR signalling pathway. miR-215-5p may serve as a novel small molecule for therapeutic intervention in psoriasis.

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