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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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2019/6768504 |
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| author | Congshan Jiang Jing Xu Wenhua Zhu Yongsong Cai Si Wang Yuanxu Guo Ke Xu Manman Geng Nazim Hussain Yan Han Fujun Zhang Qilan Ning Liesu Meng Shemin Lu |
| author_facet | Congshan Jiang Jing Xu Wenhua Zhu Yongsong Cai Si Wang Yuanxu Guo Ke Xu Manman Geng Nazim Hussain Yan Han Fujun Zhang Qilan Ning Liesu Meng Shemin Lu |
| author_sort | Congshan Jiang |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-2418e010b18b4f309afecee4207b1199 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-2418e010b18b4f309afecee4207b11992025-02-03T01:27:36ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/67685046768504Abnormal Expression of DICER1 Leads to Dysregulation of Inflammatory Effectors in Human SynoviocytesCongshan Jiang0Jing Xu1Wenhua Zhu2Yongsong Cai3Si Wang4Yuanxu Guo5Ke Xu6Manman Geng7Nazim Hussain8Yan Han9Fujun Zhang10Qilan Ning11Liesu Meng12Shemin Lu13Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, No. 76 Yanta West Road, Xi’an, Shaanxi, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, No. 76 Yanta West Road, Xi’an, Shaanxi, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, No. 76 Yanta West Road, Xi’an, Shaanxi, ChinaDepartment of Orthopedics of the First Affiliated Hospital, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, No. 76 Yanta West Road, Xi’an, Shaanxi, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, No. 76 Yanta West Road, Xi’an, Shaanxi, ChinaDepartment of Joint Surgery, Xi’an Hong Hui Hospital, Xi’an Jiaotong University Health Science Center, Xi’an, 710054, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, No. 76 Yanta West Road, Xi’an, Shaanxi, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, No. 76 Yanta West Road, Xi’an, Shaanxi, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, No. 76 Yanta West Road, Xi’an, Shaanxi, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, No. 76 Yanta West Road, Xi’an, Shaanxi, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, No. 76 Yanta West Road, Xi’an, Shaanxi, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, No. 76 Yanta West Road, Xi’an, Shaanxi, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, No. 76 Yanta West Road, Xi’an, Shaanxi, ChinaDysregulation 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.http://dx.doi.org/10.1155/2019/6768504 |
| spellingShingle | Congshan Jiang Jing Xu Wenhua Zhu Yongsong Cai Si Wang Yuanxu Guo Ke Xu Manman Geng Nazim Hussain Yan Han Fujun Zhang Qilan Ning Liesu Meng Shemin Lu Abnormal Expression of DICER1 Leads to Dysregulation of Inflammatory Effectors in Human Synoviocytes Mediators of Inflammation |
| 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 |
| url | http://dx.doi.org/10.1155/2019/6768504 |
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