miR-125b-mediated regulation of cell proliferation through the Jagged-1/Notch signaling pathway by inhibiting BRD4 expression in psoriasis

Psoriasis is a chronic inflammatory disease characterized by the abnormal differentiation and hyperproliferation of epidermal keratinocytes. The aim of the present study was to investigate the mechanism by which microRNA-125b (miR-125b) inhibits the activation of the bromodomain-containing protein 4 (BRD4)/Notch signaling pathway in psoriasis. The contents of associated miRNAs in serum samples from 32 patients with psoriasis were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The most significantly downregulated miRNA, miR-125b, was screened out. In experiments using HaCaT cells, the association between miR-125b and cell proliferation was observed using a Cell Counting Kit-8 assay, that between miR-125b and the Notch signaling pathway was observed by western blotting and RT-qPCR, and that between miR-125b and the upstream molecule BRD4 of the Notch signaling pathway was observed by luciferase reporter assay and western blotting. The proliferation of HaCaT cells became apparent following miR-125b inhibition. The Jagged-1 ligand in the Notch signaling pathway was upregulated, the active intracellular domain of the Notch1 receptor was increasingly truncated, and the Notch signaling pathway was activated. Furthermore, the inhibited miR-125b contributed directly toward the upstream protein BRD4 3 '-UTR of Jagged-1, ultimately activating the Notch signaling pathway with the upregulation of Jagged-1. In conclusion, the proliferation of HaCaT cells mediated by the Jagged-1/Notch signaling pathway was decreased with the miR-125b-mediated inhibition of BRD4 expression. Therefore, miR-125b may be a biomarker and potential therapeutic target for psoriasis treatment.