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Abnormal Expression of DICER1 Leads to Dysregulation of Inflammatory Effectors in Human Synoviocytes

Dysregulation of multiple microRNAs widely takes place during rheumatoid arthritis (RA) and experimental arthritides. This study is performed to explore the possible mechanism underlying DICER1 deficiency-mediated inflammation in human synoviocytes SW982. Firstly, RNAi of DICER1 led to increased COX...

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Autores principales: Jiang, Congshan, Xu, Jing, Zhu, Wenhua, Cai, Yongsong, Wang, Si, Guo, Yuanxu, Xu, Ke, Geng, Manman, Hussain, Nazim, Han, Yan, Zhang, Fujun, Ning, Qilan, Meng, Liesu, Lu, Shemin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558604/
https://www.ncbi.nlm.nih.gov/pubmed/31275058
http://dx.doi.org/10.1155/2019/6768504
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author Jiang, Congshan
Xu, Jing
Zhu, Wenhua
Cai, Yongsong
Wang, Si
Guo, Yuanxu
Xu, Ke
Geng, Manman
Hussain, Nazim
Han, Yan
Zhang, Fujun
Ning, Qilan
Meng, Liesu
Lu, Shemin
author_facet Jiang, Congshan
Xu, Jing
Zhu, Wenhua
Cai, Yongsong
Wang, Si
Guo, Yuanxu
Xu, Ke
Geng, Manman
Hussain, Nazim
Han, Yan
Zhang, Fujun
Ning, Qilan
Meng, Liesu
Lu, Shemin
author_sort Jiang, Congshan
collection PubMed
description Dysregulation of multiple microRNAs widely takes place during rheumatoid arthritis (RA) and experimental arthritides. This study is performed to explore the possible mechanism underlying DICER1 deficiency-mediated inflammation in human synoviocytes SW982. Firstly, RNAi of DICER1 led to increased COX2, MMP3, and MMP13 protein production, while DICER1 overexpression could reduce MMP13 expression. Secondly, the increase of IL-8 and decrease of TGF-β1 and TIMP1 were determined in the supernatant derived from DICER1 siRNA-treated cells, while DICER1 overexpression was found capable to reverse this effect. Ingenuity pathway analysis (IPA) software predicted that the Dicer1 deficiency-induced dysregulated cytokines in synoviocytes could possibly lead to the inflammatory disorders in the synovial tissue. Moreover, DICER1 deficiency could also reduce apoptosis, while DICER1 overexpression was found to decrease the proliferation and enhance apoptosis. In addition, DICER1 deficiency could lower the expression of multiple RA-related miRNAs such as miR-155. Meanwhile, DICER1 overexpression could rescue their low expression levels. And then, gain or loss of miR-155 function could regulate the protein levels of MMP3 and MMP13. These results indicated that DICER1 might play its role through regulating its downstream RA-related miRNAs. Our data demonstrated that DICER1 deficiency could cause multiple proinflammatory events in human synoviocytes SW982. This mechanism study might provide the possible target molecule to modify the inflammatory destruction and overproliferation in synoviocytes.
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spelling pubmed-65586042019-07-02 Abnormal Expression of DICER1 Leads to Dysregulation of Inflammatory Effectors in Human Synoviocytes Jiang, Congshan Xu, Jing Zhu, Wenhua Cai, Yongsong Wang, Si Guo, Yuanxu Xu, Ke Geng, Manman Hussain, Nazim Han, Yan Zhang, Fujun Ning, Qilan Meng, Liesu Lu, Shemin Mediators Inflamm Research Article Dysregulation of multiple microRNAs widely takes place during rheumatoid arthritis (RA) and experimental arthritides. This study is performed to explore the possible mechanism underlying DICER1 deficiency-mediated inflammation in human synoviocytes SW982. Firstly, RNAi of DICER1 led to increased COX2, MMP3, and MMP13 protein production, while DICER1 overexpression could reduce MMP13 expression. Secondly, the increase of IL-8 and decrease of TGF-β1 and TIMP1 were determined in the supernatant derived from DICER1 siRNA-treated cells, while DICER1 overexpression was found capable to reverse this effect. Ingenuity pathway analysis (IPA) software predicted that the Dicer1 deficiency-induced dysregulated cytokines in synoviocytes could possibly lead to the inflammatory disorders in the synovial tissue. Moreover, DICER1 deficiency could also reduce apoptosis, while DICER1 overexpression was found to decrease the proliferation and enhance apoptosis. In addition, DICER1 deficiency could lower the expression of multiple RA-related miRNAs such as miR-155. Meanwhile, DICER1 overexpression could rescue their low expression levels. And then, gain or loss of miR-155 function could regulate the protein levels of MMP3 and MMP13. These results indicated that DICER1 might play its role through regulating its downstream RA-related miRNAs. Our data demonstrated that DICER1 deficiency could cause multiple proinflammatory events in human synoviocytes SW982. This mechanism study might provide the possible target molecule to modify the inflammatory destruction and overproliferation in synoviocytes. Hindawi 2019-05-28 /pmc/articles/PMC6558604/ /pubmed/31275058 http://dx.doi.org/10.1155/2019/6768504 Text en Copyright © 2019 Congshan Jiang et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Jiang, Congshan
Xu, Jing
Zhu, Wenhua
Cai, Yongsong
Wang, Si
Guo, Yuanxu
Xu, Ke
Geng, Manman
Hussain, Nazim
Han, Yan
Zhang, Fujun
Ning, Qilan
Meng, Liesu
Lu, Shemin
Abnormal Expression of DICER1 Leads to Dysregulation of Inflammatory Effectors in Human Synoviocytes
title Abnormal Expression of DICER1 Leads to Dysregulation of Inflammatory Effectors in Human Synoviocytes
title_full Abnormal Expression of DICER1 Leads to Dysregulation of Inflammatory Effectors in Human Synoviocytes
title_fullStr Abnormal Expression of DICER1 Leads to Dysregulation of Inflammatory Effectors in Human Synoviocytes
title_full_unstemmed Abnormal Expression of DICER1 Leads to Dysregulation of Inflammatory Effectors in Human Synoviocytes
title_short Abnormal Expression of DICER1 Leads to Dysregulation of Inflammatory Effectors in Human Synoviocytes
title_sort abnormal expression of dicer1 leads to dysregulation of inflammatory effectors in human synoviocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558604/
https://www.ncbi.nlm.nih.gov/pubmed/31275058
http://dx.doi.org/10.1155/2019/6768504
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