Mesenchymal Stem Cell–Originated Exosomal Circular RNA circFBXW7 Attenuates Cell Proliferation, Migration and Inflammation of Fibroblast-Like Synoviocytes by Targeting miR-216a-3p/HDAC4 in Rheumatoid Arthritis

Mesenchymal Stem Cell–Originated Exosomal Circular RNA circFBXW7 Attenuates Cell Proliferation, Migration and Inflammation of Fibroblast-Like Synoviocytes by Targeting miR-216a-3p/HDAC4 in Rheumatoid Arthritis

Lihua Chang,1 Liang Kan2 1Department of Rheumatology and Immunology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of China; 2Department of Gerontology and Geriatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People...

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Autores principales: Chang L, Kan L
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2021
Materias:
rheumatoid arthritis
mesenchymal stem cell
fibroblast-like synoviocytes
circfbxw7
mir-216a-3p
hdac4
Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
Acceso en línea:https://doaj.org/article/81e6ae3855dd4594a9072186aeea1bf0
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spelling oai:doaj.org-article:81e6ae3855dd4594a9072186aeea1bf02021-11-23T18:43:01ZMesenchymal Stem Cell–Originated Exosomal Circular RNA circFBXW7 Attenuates Cell Proliferation, Migration and Inflammation of Fibroblast-Like Synoviocytes by Targeting miR-216a-3p/HDAC4 in Rheumatoid Arthritis1178-7031https://doaj.org/article/81e6ae3855dd4594a9072186aeea1bf02021-11-01T00:00:00Zhttps://www.dovepress.com/mesenchymal-stem-celloriginated-exosomal-circular-rna-circfbxw7-attenu-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Lihua Chang,1 Liang Kan2 1Department of Rheumatology and Immunology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of China; 2Department of Gerontology and Geriatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of ChinaCorrespondence: Liang KanDepartment of Gerontology and Geriatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of ChinaEmail kanliang31cmu@163.comBackground: Rheumatoid arthritis (RA) is a chronic autoimmune disease of articular joint damage and elevated synovial hyperplasia. Abnormal proliferation, invasion inflammatory response of rheumatoid fibroblast-like synoviocytes (RA-FLS) play a critical role in RA progression. Mesenchymal stem cell (MSC)–derived exosomal circular RNAs are promising therapeutic manner for disease treatment. This work aimed to decipher the role of exosomal circFBXW7 in RA.Methods: The expression of circFBXW7, miR-216a-3p, and HDAC4 were detected in clinical RA samples. The RA rat model was established. Isolation and identification of exosomes from MSCs was conducted. The effects of exosomal circFBXW7 on RA was evaluated by qPCR, CCK-8, transwell assays, flow cytometry, Western blotting, ELISA, and immunohistochemical assay. Interaction between miR-216a-3p and circFBXW7 or HDAC4 was determined by luciferase reporter gene assay and RNA pulldown.Results: Exosomal circFBXW7 treatment suppressed proliferation, migration and inflammatory response of RA-FLSs and damage of RA model. CircFBXW7 could directly sponge miR-216a-3p to upregulate the expression of HDAC4. Inhibition of HDAC4 or upregulation of miR-216a-3p abolished the therapeutic function of exosomal circFBXW7. Our data demonstrated that circFBXW7 and HDAC4 were decreased, and miR-216a-3p was elevated in clinical RA sample compared with healthy samples.Conclusion: We concluded that MSC-derived exosomal circFBXW7 suppressed proliferation, migration and inflammatory response of RA-FLSs and damage of RA rats via sponging miR-216a-3p and release the activation of HDAC4. These findings may provide a novel therapeutic target for RA.Keywords: rheumatoid arthritis, mesenchymal stem cell, fibroblast-like synoviocytes, circFBXW7, miR-216a-3p, HDAC4Chang LKan LDove Medical Pressarticlerheumatoid arthritismesenchymal stem cellfibroblast-like synoviocytescircfbxw7mir-216a-3phdac4PathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 6157-6171 (2021)
institution DOAJ
collection DOAJ
language EN
topic rheumatoid arthritis
mesenchymal stem cell
fibroblast-like synoviocytes
circfbxw7
mir-216a-3p
hdac4
Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
spellingShingle rheumatoid arthritis
mesenchymal stem cell
fibroblast-like synoviocytes
circfbxw7
mir-216a-3p
hdac4
Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
Chang L
Kan L
Mesenchymal Stem Cell–Originated Exosomal Circular RNA circFBXW7 Attenuates Cell Proliferation, Migration and Inflammation of Fibroblast-Like Synoviocytes by Targeting miR-216a-3p/HDAC4 in Rheumatoid Arthritis
description Lihua Chang,1 Liang Kan2 1Department of Rheumatology and Immunology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of China; 2Department of Gerontology and Geriatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of ChinaCorrespondence: Liang KanDepartment of Gerontology and Geriatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of ChinaEmail kanliang31cmu@163.comBackground: Rheumatoid arthritis (RA) is a chronic autoimmune disease of articular joint damage and elevated synovial hyperplasia. Abnormal proliferation, invasion inflammatory response of rheumatoid fibroblast-like synoviocytes (RA-FLS) play a critical role in RA progression. Mesenchymal stem cell (MSC)–derived exosomal circular RNAs are promising therapeutic manner for disease treatment. This work aimed to decipher the role of exosomal circFBXW7 in RA.Methods: The expression of circFBXW7, miR-216a-3p, and HDAC4 were detected in clinical RA samples. The RA rat model was established. Isolation and identification of exosomes from MSCs was conducted. The effects of exosomal circFBXW7 on RA was evaluated by qPCR, CCK-8, transwell assays, flow cytometry, Western blotting, ELISA, and immunohistochemical assay. Interaction between miR-216a-3p and circFBXW7 or HDAC4 was determined by luciferase reporter gene assay and RNA pulldown.Results: Exosomal circFBXW7 treatment suppressed proliferation, migration and inflammatory response of RA-FLSs and damage of RA model. CircFBXW7 could directly sponge miR-216a-3p to upregulate the expression of HDAC4. Inhibition of HDAC4 or upregulation of miR-216a-3p abolished the therapeutic function of exosomal circFBXW7. Our data demonstrated that circFBXW7 and HDAC4 were decreased, and miR-216a-3p was elevated in clinical RA sample compared with healthy samples.Conclusion: We concluded that MSC-derived exosomal circFBXW7 suppressed proliferation, migration and inflammatory response of RA-FLSs and damage of RA rats via sponging miR-216a-3p and release the activation of HDAC4. These findings may provide a novel therapeutic target for RA.Keywords: rheumatoid arthritis, mesenchymal stem cell, fibroblast-like synoviocytes, circFBXW7, miR-216a-3p, HDAC4
format article
author Chang L
Kan L
author_facet Chang L
Kan L
author_sort Chang L
title Mesenchymal Stem Cell–Originated Exosomal Circular RNA circFBXW7 Attenuates Cell Proliferation, Migration and Inflammation of Fibroblast-Like Synoviocytes by Targeting miR-216a-3p/HDAC4 in Rheumatoid Arthritis
title_short Mesenchymal Stem Cell–Originated Exosomal Circular RNA circFBXW7 Attenuates Cell Proliferation, Migration and Inflammation of Fibroblast-Like Synoviocytes by Targeting miR-216a-3p/HDAC4 in Rheumatoid Arthritis
title_full Mesenchymal Stem Cell–Originated Exosomal Circular RNA circFBXW7 Attenuates Cell Proliferation, Migration and Inflammation of Fibroblast-Like Synoviocytes by Targeting miR-216a-3p/HDAC4 in Rheumatoid Arthritis
title_fullStr Mesenchymal Stem Cell–Originated Exosomal Circular RNA circFBXW7 Attenuates Cell Proliferation, Migration and Inflammation of Fibroblast-Like Synoviocytes by Targeting miR-216a-3p/HDAC4 in Rheumatoid Arthritis
title_full_unstemmed Mesenchymal Stem Cell–Originated Exosomal Circular RNA circFBXW7 Attenuates Cell Proliferation, Migration and Inflammation of Fibroblast-Like Synoviocytes by Targeting miR-216a-3p/HDAC4 in Rheumatoid Arthritis
title_sort mesenchymal stem cell–originated exosomal circular rna circfbxw7 attenuates cell proliferation, migration and inflammation of fibroblast-like synoviocytes by targeting mir-216a-3p/hdac4 in rheumatoid arthritis
publisher Dove Medical Press
publishDate 2021
url https://doaj.org/article/81e6ae3855dd4594a9072186aeea1bf0
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AT kanl mesenchymalstemcellndashoriginatedexosomalcircularrnacircfbxw7attenuatescellproliferationmigrationandinflammationoffibroblastlikesynoviocytesbytargetingmir216a3phdac4inrheumatoidarthritis
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