FOXC1‑mediated TRIM22 regulates the excessive proliferation and inflammation of fibroblast‑like synoviocytes in rheumatoid arthritis via NF‑κB signaling pathway

Wei,Yazhi; Huang,Xinmin; Ma,Yanmei; Dai,Liping

doi:10.3892/mmr.2022.12820

FOXC1‑mediated TRIM22 regulates the excessive proliferation and inflammation of fibroblast‑like synoviocytes in rheumatoid arthritis via NF‑κB signaling pathway

Authors:
- Yazhi Wei
- Xinmin Huang
- Yanmei Ma
- Liping Dai
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Affiliations: Department of Clinical Laboratory, Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, Guangdong 518040, P.R. China, Department of Rheumatology, Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, Guangdong 518040, P.R. China, The Science and education division, Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, Guangdong 518040, P.R. China
Published online on: August 9, 2022 https://doi.org/10.3892/mmr.2022.12820
Article Number: 304
Copyright: © Wei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Rheumatoid arthritis (RA) is a common systemic autoimmune disorder of unknown etiology, which threatens public health. The regulatory role of tripartite motif‑containing 22 (TRIM22) has been reported in multiple types of cancers and disease, but not in RA. The aim of the present study was therefore to elucidate the potential roles and underlying mechanisms of TRIM22 in fibroblast‑like synoviocytes (FLSs) in RA. The Gene Expression Omnibus database was used to examine TRIM22 mRNA expression levels in synovial tissue samples of patients with RA and healthy controls. TRIM22 and forkhead box C1 (FOXC1) mRNA and protein expression levels in normal FLSs and RA‑FLSs were assessed using reverse transcription‑quantitative PCR (RT‑qPCR) and western blotting, respectively. The Cell Counting Kit‑8 assay was used to assess cell proliferation. Cell apoptosis was analyzed using flow cytometry. The migratory and invasive abilities of RA‑FLSs were assessed using Transwell assays. Western blotting was used to analyze the protein expression levels of apoptosis‑related factors, MMP2, MMP9 and NF‑κB signaling pathway‑related proteins. Inflammatory factors levels were assessed via ELISA and RT‑qPCR. Furthermore, the JASPAR database, chromatin immunoprecipitation and the dual‑luciferase reporter assays were used to determine the interaction between FOXC1 and the TRIM22 promoter. The results of the present study demonstrated that TRIM22 expression levels were significantly elevated in the synovial tissue samples of patients with RA and RA‑FLSs. Moreover, FOXC1 was also significantly overexpressed in RA‑FLSs. TRIM22 knockdown significantly reduced cell proliferation, migration, invasion and the inflammatory response, whereas cell apoptosis was significantly increased. Furthermore, the results demonstrated that FOXC1 may have positively mediated TRIM22 expression via binding to the TRIM22 promoter. Moreover, FOXC1 overexpression significantly reversed the outcome of TRIM22 knockdown on the proliferation, apoptosis, migration, invasion and inflammation of RA‑FLSs. FOXC1 overexpression also significantly reversed the inactivation of the NF‑κB signaling pathway caused by TRIM22 knockdown. In summary, the present study demonstrated that TRIM22 was potentially activated via FOXC1, which contributed to the progression of RA via the NF‑κB signaling pathway.

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