MiRNA-6089 inhibits rheumatoid arthritis fibroblast-like synoviocytes proliferation and induces apoptosis by targeting CCR4

Suxian Lin,Shengnan Wang,Zhiyong Zhang,Yang Lu,Meilv Yang,Ping Chen,Lianguo Chen,Mudan Wang

doi:10.1080/13813455.2020.1773862

Abstract

Several studies have suggested that fibroblast-like synoviocytes (FLSs) and miRNAs are implicated in the pathogenesis of rheumatoid arthritis (RA). This study was aimed to evaluate the function of miR-6089 in the regulation of RA-FLSs. The levels of miR-6089 were detected to be significantly lower in the synovial tissues and FLSs of RA than in the healthy synovial tissues and FLSs. The miR-6089 up-regulation in RA-FLSs significantly inhibited the proliferation and promoted cell apoptosis accompany with an increase protein expression of cleaved-Caspase-3, -8 and -9. Furthermore, CCR4 was determined to target miR-6089 directly, and its expression was significantly increased in the synovial tissues of RA than in the healthy synovial tissues. The overexpression of CCR4 reversed the effect of miR-6089 on proliferation and apoptosis in RA-FLSs effectively. In conclusion, our study suggests that the miR-6089 may be a potential target for prevention and treatment of RA.

Highlights

Growing data have indicated that fibroblast-like synoviocytes (FLS) and miRNAs are implicated in the pathogenesis of rheumatoid arthritis (RA)
Our results revealed that miR-6089 may be a potential target for RA prevention and therapy of RA
The expression levels of miR-6089 were significantly lower in synovial tissues of RA patients versus the healthy controls (P < 0.01; Fig. 1A)

Summary

Introduction

Growing data have indicated that fibroblast-like synoviocytes (FLS) and miRNAs are implicated in the pathogenesis of rheumatoid arthritis (RA). This study was aimed to evaluate the function of miR-6089 in the regulation of RA-FLSs. Rheumatoid arthritis (RA) is a chronic, progressive, systemic, inflammatory joint disease characterized by synovial hyperplasia, inflammation, cartilage degradation, and bone destruction of unknown etiology[1]. The number of cases in developing countries reaches 5–50 per 100,000, while the incidence of adults in developed countries reaches 0.5% -1%[2]. It is well known that the abnormal activation of fibroblast-like synoviocytes (FLS) plays an important role in the initial stages of synovial inflammation and joint destruction as well as in the progressive development stage[5, 6]. It is essential to identify novel biomarkers of RA progression in order to improve therapeutic strategies

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Conclusion