Circ_0000396 inhibits rheumatoid arthritis synovial fibroblast growth and inflammatory response via miR-203/HBP1 axis

Abstract Background Circ_0000396 was found to be down-regulated in the rheumatoid arthritis (RA) patients and had a high diagnostic value. However, the function and mechanisms underlying circ_0000396 in RA progression remain unclear. Methods The expression of circ_0000396, microRNA (miR)-203 and HMG...

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Main Authors: Laifang Wang, Qing Zhao, Na Wang, Yanjie Ding, Lingli Kong, Jing Wang
Format: Article
Language:English
Published: Aristotle University of Thessaloniki 2021-01-01
Series:Journal of Biological Research - Thessaloniki
Subjects:
Online Access:https://doi.org/10.1186/s40709-020-00131-4
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author Laifang Wang
Qing Zhao
Na Wang
Yanjie Ding
Lingli Kong
Jing Wang
author_facet Laifang Wang
Qing Zhao
Na Wang
Yanjie Ding
Lingli Kong
Jing Wang
author_sort Laifang Wang
collection DOAJ
description Abstract Background Circ_0000396 was found to be down-regulated in the rheumatoid arthritis (RA) patients and had a high diagnostic value. However, the function and mechanisms underlying circ_0000396 in RA progression remain unclear. Methods The expression of circ_0000396, microRNA (miR)-203 and HMG-box transcription factor 1 (HBP1) was detected using qRT-PCR and western blot. The proliferative and apoptotic capabilities of rheumatoid arthritis synovial fibroblasts (RASFs) were measured by colony formation, CCK-8, flow cytometry and western blot assays, respectively. The levels of interleukins (IL)-6, IL-1β, IL-8 and tumor necrosis factor-α (TNF-α) were detected using enzyme-linked immunosorbent assay (ELISA). The target correlations between miR-203 and circ_0000396 or HBP1 were validated using pull-down and dual-luciferase reporter assay. Results Circ_0000396 was decreased in RA synovial tissues and RASFs, and overexpression of circ_0000396 suppressed cell proliferation, induced cell apoptosis and reduced the release of inflammatory cytokine IL-6, IL-1β, IL-8 and TNF-α in RASFs, while circ_0000396 deletion functioned oppositely. MiR-203 was confirmed to be a target of circ_0000396, and miR-203 reversed the protective effects of circ_0000396 on the dysfunction and inflammation of RASFs. HBP1 was a target of miR-203, and silencing miR-203 inhibited RASFs malignant changes by regulating HBP1. In addition, circ_0000396 could regulate HBP1 by sponging miR-203, and HBP1 decrease attenuated the effects of circ_0000396 on RASF growth and inflammation. Conclusion Circ_0000396 inhibited the growth and inflammation in RASFs by regulating miR-203/HBP1 axis, providing a potential therapeutic target for RA.
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spelling doaj.art-6fa6ae5ee36a4e46916e73031231ed8a2022-12-22T02:38:54ZengAristotle University of ThessalonikiJournal of Biological Research - Thessaloniki2241-57932021-01-0128111110.1186/s40709-020-00131-4Circ_0000396 inhibits rheumatoid arthritis synovial fibroblast growth and inflammatory response via miR-203/HBP1 axisLaifang Wang0Qing Zhao1Na Wang2Yanjie Ding3Lingli Kong4Jing Wang5Department of Rheumatism and Immunology, Huaihe Hospital of Henan UniversityDepartment of Rheumatism and Immunology, Huaihe Hospital of Henan UniversityDepartment of Rheumatism and Immunology, Huaihe Hospital of Henan UniversityDepartment of Rheumatism and Immunology, Huaihe Hospital of Henan UniversityDepartment of Rheumatism and Immunology, Huaihe Hospital of Henan UniversityDepartment of Rheumatism and Immunology, Huaihe Hospital of Henan UniversityAbstract Background Circ_0000396 was found to be down-regulated in the rheumatoid arthritis (RA) patients and had a high diagnostic value. However, the function and mechanisms underlying circ_0000396 in RA progression remain unclear. Methods The expression of circ_0000396, microRNA (miR)-203 and HMG-box transcription factor 1 (HBP1) was detected using qRT-PCR and western blot. The proliferative and apoptotic capabilities of rheumatoid arthritis synovial fibroblasts (RASFs) were measured by colony formation, CCK-8, flow cytometry and western blot assays, respectively. The levels of interleukins (IL)-6, IL-1β, IL-8 and tumor necrosis factor-α (TNF-α) were detected using enzyme-linked immunosorbent assay (ELISA). The target correlations between miR-203 and circ_0000396 or HBP1 were validated using pull-down and dual-luciferase reporter assay. Results Circ_0000396 was decreased in RA synovial tissues and RASFs, and overexpression of circ_0000396 suppressed cell proliferation, induced cell apoptosis and reduced the release of inflammatory cytokine IL-6, IL-1β, IL-8 and TNF-α in RASFs, while circ_0000396 deletion functioned oppositely. MiR-203 was confirmed to be a target of circ_0000396, and miR-203 reversed the protective effects of circ_0000396 on the dysfunction and inflammation of RASFs. HBP1 was a target of miR-203, and silencing miR-203 inhibited RASFs malignant changes by regulating HBP1. In addition, circ_0000396 could regulate HBP1 by sponging miR-203, and HBP1 decrease attenuated the effects of circ_0000396 on RASF growth and inflammation. Conclusion Circ_0000396 inhibited the growth and inflammation in RASFs by regulating miR-203/HBP1 axis, providing a potential therapeutic target for RA.https://doi.org/10.1186/s40709-020-00131-4circ_0000396Rheumatoid arthritisSynovial fibroblastsmiR-203; HBP1
spellingShingle Laifang Wang
Qing Zhao
Na Wang
Yanjie Ding
Lingli Kong
Jing Wang
Circ_0000396 inhibits rheumatoid arthritis synovial fibroblast growth and inflammatory response via miR-203/HBP1 axis
Journal of Biological Research - Thessaloniki
circ_0000396
Rheumatoid arthritis
Synovial fibroblasts
miR-203; HBP1
title Circ_0000396 inhibits rheumatoid arthritis synovial fibroblast growth and inflammatory response via miR-203/HBP1 axis
title_full Circ_0000396 inhibits rheumatoid arthritis synovial fibroblast growth and inflammatory response via miR-203/HBP1 axis
title_fullStr Circ_0000396 inhibits rheumatoid arthritis synovial fibroblast growth and inflammatory response via miR-203/HBP1 axis
title_full_unstemmed Circ_0000396 inhibits rheumatoid arthritis synovial fibroblast growth and inflammatory response via miR-203/HBP1 axis
title_short Circ_0000396 inhibits rheumatoid arthritis synovial fibroblast growth and inflammatory response via miR-203/HBP1 axis
title_sort circ 0000396 inhibits rheumatoid arthritis synovial fibroblast growth and inflammatory response via mir 203 hbp1 axis
topic circ_0000396
Rheumatoid arthritis
Synovial fibroblasts
miR-203; HBP1
url https://doi.org/10.1186/s40709-020-00131-4
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