MiR-128-3p promotes hyperproliferation of keratinocytes and psoriasis-like inflammation by targeting SIRT1/HIF-1α.

Psoriasis is a long-lasting inflammatory skin condition characterized by excessive keratinocyte growth. Recent studies have confirmed abnormal regulation of microRNAs (miRNAs/miRs) in individuals with psoriasis. This study aimed to investigate the function and specific mechanism of action of miR-128a-3p in interleukin-22 (IL-22)-stimulated HaCaT cells. The expression level of miR-128-3p and sirtuin 1 (SIRT1)/hypoxia inducible factor (HIF-1α) was detected using qRT-PCR on patients with psoriasis and IL-22-treated HaCaT cell model. Western blotting was used to detect apoptosis-associated proteins and SIRT1/HIFα pathway protein expression levels. The cell viability was determined using the CCK-8 method. Flow cytometry was performed to detect apoptosis following IL-22 stimulation or transfection. Enzyme-linked immunosorbent assay (ELISA) was used to detect cellular inflammatory factor secretion. The relationship between miR-128-3p and SIRT1 was predicted using the Starbase database and verified using a dual-luciferase reporter gene assay. In patients with psoriasis and IL-22-stimulated HaCaT cells, miR-128-3p and HIF-1α expression levels were elevated and SIRT1 expression was decreased. miR-128-3p directly targeted SIRT1. IL-22 stimulation significantly elevated cell viability, inhibited apoptosis levels and cleaved-caspase3 protein expression, and promoted an inflammatory response in HaCaT cells, which was further promoted by the miR-128-3p mimic. The miR-128-3p inhibitor reduced cell viability, promoted cell apoptosis and cleaved-caspase3 protein expression, and inhibited the inflammatory response in IL-22-induced HaCaT cells; these effects were at least partly reversed by SIRT1-siRNA. miR-128-3p expression is elevated in psoriasis and promotes psoriasis progression by inhibiting SIRT1 expression.