MicroRNA‑23a‑5p regulates cell proliferation, migration and inflammation of TNF‑α‑stimulated human fibroblast‑like MH7A synoviocytes by targeting TLR4 in rheumatoid arthritis

Bao,Xiao; Ma,Ling; He,Chengsong

doi:10.3892/etm.2021.9910

MicroRNA‑23a‑5p regulates cell proliferation, migration and inflammation of TNF‑α‑stimulated human fibroblast‑like MH7A synoviocytes by targeting TLR4 in rheumatoid arthritis

Authors:
- Xiao Bao
- Ling Ma
- Chengsong He
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Affiliations: Department of Rheumatology and Immunology, The People's Hospital of De Yang City, Deyang, Sichuan 618000, P.R. China, Department of Rheumatology and Immunology, Southwest Medical University Affiliated Hospital, Luzhou, Sichuan 646000, P.R. China
Published online on: March 12, 2021 https://doi.org/10.3892/etm.2021.9910
Article Number: 479
Copyright: © Bao 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 chronic inflammatory disease characterized by synovial joint inflammation. RA synovial fibroblasts (RASFs) constitute a major cell subset of the RA synovia. MicroRNAs (miRNAs/miRs) have been reported to serve a role in the activation and proliferation of RASFs. The present study aimed to investigate the effects and underlying mechanisms of miR‑23a‑5p on RA progression. Peripheral blood was collected from patients with RA (n=20) to analyze the expression levels of miR‑23a‑5p. The effects of miR‑23a‑5p on cell apoptosis, proliferation and migration in MH7A cells were determined in TNF‑α‑treated human fibroblast‑like synoviocytes (MH7A cells) by flow cytometry, colony formation assay and Transwell assay, respectively. The cell cycle distribution was evaluated using flow cytometry. The binding relationship between miR‑23a‑5p and toll‑like receptor (TLR) 4 was analyzed using a dual luciferase reporter gene assay. ELISA and reverse transcription‑quantitative PCR assays were used to detect the levels of the inflammatory factors IL‑6, IL‑1β and IL‑10. The expression levels of apoptosis‑ and migration‑related proteins were analyzed using western blotting. The results of the present study revealed that the expression levels of miR‑23a‑5p were significantly downregulated in the plasma of patients with RA and in MH7A cells. In addition, the TNF‑α‑induced increase in the cell proliferative and migratory rates and the production of IL‑6 and IL‑1β were markedly inhibited following miR‑23a‑5p overexpression. The TNF‑α‑induced decreases in MH7A cell apoptosis were also reversed following miR‑23a‑5p overexpression. Additionally, transfection with miR‑23a‑5p mimics significantly inhibited the activation of the TLR4/NF‑κB signaling pathway in TNF‑α‑treated MH7A cells by targeting TLR4. Notably, TLR4 overexpression weakened the effects of miR‑23a‑5p mimic on cell proliferation, apoptosis, migration, inflammation and the TLR4/NF‑κB signaling pathway in TNF‑α‑induced MH7A cells. In conclusion, the findings of the present study indicated that the miR‑23a‑5p/TLR4/NF‑κB axis may serve as a promising target for RA diagnosis and treatment.

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