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H19 increases IL-17A/IL-23 releases via regulating VDR by interacting with miR675-5p/miR22-5p in ankylosing spondylitis

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Zhang, X, Ji, S, Cai, G ORCID: 0000-0002-6481-704X, Pan, Z, Han, R, Yuan, Y, Xu, S, Yang, J, Hu, X, Chen, M, Wu, M, Ma, Y, Deng, J, Gao, X, Guan, S, Xu, S, Shuai, Z, Laslett, L ORCID: 0000-0002-4336-0095 and Pan, F 2020 , 'H19 increases IL-17A/IL-23 releases via regulating VDR by interacting with miR675-5p/miR22-5p in ankylosing spondylitis' , Molecular Therapy - Nucleic Acids, vol. 19 , pp. 393-404 , doi: 10.1016/j.omtn.2019.11.025.

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Abstract

Long non-coding RNA (lncRNA) H19 is associated with inflammatory diseases, but the molecular mechanism of H19 in the inflammatory process of ankylosing spondylitis (AS) is unclear. Here, we investigated the role of H19 and its downstream molecules in the inflammation of AS by microarray analysis, qRT-PCR, western blot, and dual-luciferase reporter assay. H19 small interfering RNA (siRNA) (Si-H19) and adenovirus (AD-H19) were used to decrease and increase H19 expression, respectively. 42 annotated lncRNAs were identified, and H19 was overexpressed. H19, vitamin D receptor (VDR), and transforming growth factor β (TGF-β) can bind to microRNA22-5p (miR22-5p) and miR675-5p. Si-H19 significantly downregulated miR22-5p and upregulated miR675-5p expression; Si-H19 decreased the protein and mRNA expression of VDR and decreased the cytokine and mRNA levels of interleukin-17A (IL-17A) and IL-23. These results were verified by AD-H19. In addition, miR22-5p and miR675-5p inhibitors increased the protein and mRNA expression of VDR and increased the cytokine and mRNA levels of IL-17A and IL-23. These results were also confirmed by miRNA mimics. Furthermore, H19 directly interfered with miR22-5p and miR675-5p expression, whereas the two miRNAs directly inhibited VDR expression. Overall, the H19-miR22-5p/miR675-5p-VDR-IL-17A/IL-23 signaling pathways have important roles in the pathogenesis of AS.

Item Type: Article
Authors/Creators:Zhang, X and Ji, S and Cai, G and Pan, Z and Han, R and Yuan, Y and Xu, S and Yang, J and Hu, X and Chen, M and Wu, M and Ma, Y and Deng, J and Gao, X and Guan, S and Xu, S and Shuai, Z and Laslett, L and Pan, F
Keywords: H19, IL-17A, IL-23, VDR, ankylosing spondylitis, cytokines, miR22, miR675, non-coding RNA
Journal or Publication Title: Molecular Therapy - Nucleic Acids
Publisher: Cell Press
ISSN: 2162-2531
DOI / ID Number: 10.1016/j.omtn.2019.11.025
Copyright Information:

Copyright 2019 The Authors. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) https://creativecommons.org/licenses/by-nc-nd/4.0/

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