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

Pan,Min; Huang,Yao; Zhu,Xiaofang; Lin,Xiangfei; Luo,Dan

doi:10.3892/mmr.2019.10187

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

Authors:
- Min Pan
- Yao Huang
- Xiaofang Zhu
- Xiangfei Lin
- Dan Luo
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Affiliations: Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Institute of Sport Medicine, Affiliated Hospital of Nanjing University of TCM, Nanjing, Jiangsu 210023, P.R. China, Department of Dermatology, Northern Jiangsu Province Hospital, Yangzhou, Jiangsu 225001, P.R. China
Published online on: April 24, 2019 https://doi.org/10.3892/mmr.2019.10187
Pages: 5227-5236
Copyright: © Pan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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