MicroRNA-4423-3p inhibits proliferation of fibroblast-like synoviocytes by targeting matrix metalloproteinase 13 in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that is increasing in incidence worldwide. RA is regulated by a variety of microRNAs (miRNAs/miR). Moreover, analysis of public data has revealed that miR-4423-3p is significantly downregulated in peripheral blood mononuclear cel...

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Autores principales: Weihong Xu, Lu Ye, Huaxiang Wu
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Publicado: Taylor & Francis Group 2021
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Acceso en línea:https://doaj.org/article/d4763d89a8324655ba80ebdb7c0149e0
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spelling oai:doaj.org-article:d4763d89a8324655ba80ebdb7c0149e02021-12-01T14:41:00ZMicroRNA-4423-3p inhibits proliferation of fibroblast-like synoviocytes by targeting matrix metalloproteinase 13 in rheumatoid arthritis2165-59792165-598710.1080/21655979.2021.1988372https://doaj.org/article/d4763d89a8324655ba80ebdb7c0149e02021-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.1988372https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that is increasing in incidence worldwide. RA is regulated by a variety of microRNAs (miRNAs/miR). Moreover, analysis of public data has revealed that miR-4423-3p is significantly downregulated in peripheral blood mononuclear cells of RA patients. This study investigated the role of miR-4423-3p in RA. The levels of miR-4423-3p and matrix metalloproteinase 13 (MMP13) in RA patients and the regulatory relationship between miR-4423-3p and MMP13 were analyzed using public data. A dual-luciferase reporter assay was performed to verify that miR-4423-3p targets MMP13 in human fibroblast-like synoviocyte (HFLS) RA cells (HFLS-RA). Following the overexpression of miR-4423-3p, miR-4423-3p inhibitor, and MMP13 in HFLS-RA, viability, proliferation, cell cycle, apoptosis, and invasion/migration assays were used to detect the effects of miR-4423-3p targeting MMP13 on cell biological processes. The results revealed that miR-4423-3p was downregulated in peripheral blood mononuclear cells of RA patients and MMP13 was upregulated in synovial tissue of RA patients. miR-4423-3p targets the 3ʹ untranslated region of MMP13 and downregulates MMP13 expression. After overexpression of miR-4423-3p, cell proliferation, migration, and invasion were inhibited, the cell cycle was prevented and cell apoptosis was promoted. Overexpression of MMP13 promoted cell proliferation, migration, and invasion, while accelerating the cell cycle process and suppressing apoptosis. The findings indicate that in HFLS-RA cells, overexpression of miR-4423-3p inhibited proliferation, migration, and invasion, and promoted apoptosis by negatively regulating MMP13. The overexpression of miR-4423-3p might be a novel strategy for the treatment of RA.Weihong XuLu YeHuaxiang WuTaylor & Francis Grouparticlerheumatoid arthritismicrornammp13fibroblast-like synoviocytesBiotechnologyTP248.13-248.65ENBioengineered, Vol 12, Iss 2, Pp 9411-9423 (2021)
institution DOAJ
collection DOAJ
language EN
topic rheumatoid arthritis
microrna
mmp13
fibroblast-like synoviocytes
Biotechnology
TP248.13-248.65
spellingShingle rheumatoid arthritis
microrna
mmp13
fibroblast-like synoviocytes
Biotechnology
TP248.13-248.65
Weihong Xu
Lu Ye
Huaxiang Wu
MicroRNA-4423-3p inhibits proliferation of fibroblast-like synoviocytes by targeting matrix metalloproteinase 13 in rheumatoid arthritis
description Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that is increasing in incidence worldwide. RA is regulated by a variety of microRNAs (miRNAs/miR). Moreover, analysis of public data has revealed that miR-4423-3p is significantly downregulated in peripheral blood mononuclear cells of RA patients. This study investigated the role of miR-4423-3p in RA. The levels of miR-4423-3p and matrix metalloproteinase 13 (MMP13) in RA patients and the regulatory relationship between miR-4423-3p and MMP13 were analyzed using public data. A dual-luciferase reporter assay was performed to verify that miR-4423-3p targets MMP13 in human fibroblast-like synoviocyte (HFLS) RA cells (HFLS-RA). Following the overexpression of miR-4423-3p, miR-4423-3p inhibitor, and MMP13 in HFLS-RA, viability, proliferation, cell cycle, apoptosis, and invasion/migration assays were used to detect the effects of miR-4423-3p targeting MMP13 on cell biological processes. The results revealed that miR-4423-3p was downregulated in peripheral blood mononuclear cells of RA patients and MMP13 was upregulated in synovial tissue of RA patients. miR-4423-3p targets the 3ʹ untranslated region of MMP13 and downregulates MMP13 expression. After overexpression of miR-4423-3p, cell proliferation, migration, and invasion were inhibited, the cell cycle was prevented and cell apoptosis was promoted. Overexpression of MMP13 promoted cell proliferation, migration, and invasion, while accelerating the cell cycle process and suppressing apoptosis. The findings indicate that in HFLS-RA cells, overexpression of miR-4423-3p inhibited proliferation, migration, and invasion, and promoted apoptosis by negatively regulating MMP13. The overexpression of miR-4423-3p might be a novel strategy for the treatment of RA.
format article
author Weihong Xu
Lu Ye
Huaxiang Wu
author_facet Weihong Xu
Lu Ye
Huaxiang Wu
author_sort Weihong Xu
title MicroRNA-4423-3p inhibits proliferation of fibroblast-like synoviocytes by targeting matrix metalloproteinase 13 in rheumatoid arthritis
title_short MicroRNA-4423-3p inhibits proliferation of fibroblast-like synoviocytes by targeting matrix metalloproteinase 13 in rheumatoid arthritis
title_full MicroRNA-4423-3p inhibits proliferation of fibroblast-like synoviocytes by targeting matrix metalloproteinase 13 in rheumatoid arthritis
title_fullStr MicroRNA-4423-3p inhibits proliferation of fibroblast-like synoviocytes by targeting matrix metalloproteinase 13 in rheumatoid arthritis
title_full_unstemmed MicroRNA-4423-3p inhibits proliferation of fibroblast-like synoviocytes by targeting matrix metalloproteinase 13 in rheumatoid arthritis
title_sort microrna-4423-3p inhibits proliferation of fibroblast-like synoviocytes by targeting matrix metalloproteinase 13 in rheumatoid arthritis
publisher Taylor & Francis Group
publishDate 2021
url https://doaj.org/article/d4763d89a8324655ba80ebdb7c0149e0
work_keys_str_mv AT weihongxu microrna44233pinhibitsproliferationoffibroblastlikesynoviocytesbytargetingmatrixmetalloproteinase13inrheumatoidarthritis
AT luye microrna44233pinhibitsproliferationoffibroblastlikesynoviocytesbytargetingmatrixmetalloproteinase13inrheumatoidarthritis
AT huaxiangwu microrna44233pinhibitsproliferationoffibroblastlikesynoviocytesbytargetingmatrixmetalloproteinase13inrheumatoidarthritis
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