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Abstract
Background: Rheumatoid arthritis (RA) is a systematic autoimmune disease which may lead to joint dysfunction and disability. Aberrant migration and invasion of fibroblast-like synoviocytes (FLSs) is one of the most predominant etiopathogenesis of RA. Quercetin is a bioflavonoid which is implicated in the development of RA, yet its role in regulating the migration and invasion of FLSs is still elusive. The aim of this study is to investigate the impact of quercetin treatment on migration and invasion of FLSs and the underlying mechanism.
Methods: Capacity of migration and invasion of FLSs were assessed using transwell assay. Immunofluorescence assay was used to determine the expression of F-actin. The RNA levels of miR-146a and GATA transcription factor 6 (GATA6) were measured using quantitative real-time PCR. Western blot was used to examine the protein level of GATA6. The correlation between miR-146a and GATA6 was validated using luciferase reporter assay.
Results: Transwell assay revealed that the migration and invasion of FLSs were significantly inhibited after quercetin treatment, which was also proved by decreased expression of F-actin. The RNA level of miR-146a was decreased in RA tissues and was negatively related to the expression of GATA transcription factor 6 (GATA6). Quercetin treatment elevated the RNA level of miR-146a, but suppressed the expression of GATA6 in FLSs. Further luciferase reporter assay validated that GATA6 is a downstream target of miR-146a. Besides, miR-146a inhibited the migration and invasion of FLSs, and further GATA6 over-expression abrogated the miR-146a-induced inhibition. In addition, specific anti-miR-146a inhibitor abolished quercetin-mediated suppression of migration and invasion of FLSs.
Conclusion: Our study suggested that quercetin suppresses the migration and invasion of FLSs via regulating the miR-146a/GATA6 axis.
Disclosure statement
The authors declare that they have no competing interests, and all authors should confirm its accuracy.
Author contributions
JYZ and BC conceived and designed the experiments, XDP and CYW analyzed and interpreted the results of the experiments, KJW, FXH and JX performed the experiments.
Ethics approval and consent to participate
All patients were informed before sample collection, and all relative experiments were performed ethical guidelines of the Declaration of Helsinki and approved by the 940th Hospital of Joint logistics Support Force of People’s Liberation Army.
Availability of data and materials
All data generated or analyzed during this study are included in this published article.