miR-135a-5p mediated down-regulation of STAT6 inhibits proliferation and induces apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis

miR-135a-5p 介导的 STAT6 下调抑制类风湿关节炎成纤维细胞样滑膜细胞增殖并诱导其凋亡

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作者:Jiajia Liu, Jianhua Xue, Bo Xu, Junbo Yu, Yuxuan Zhang, Lili Qin, Aixian Zhang, Yang Yang

Conclusion

miR-135a-5p/STAT6 is a potential novel therapeutic target for RA treatment.

Methods

Synovial tissues from rheumatoid arthritis (RA) patients and normal participants were acquired. Cell viability, proliferation, apoptosis, concentrations of cytokines, miRNA and protein levels, and relative luciferase activities were detected.

Objective

Rheumatoid arthritis (RA), as a chronic autoimmune disorder, seriously threatens human health. However, no study has thoroughly illustrated the etiology of RA. The present work focused on investigating the biological functions of STAT6 and the upstream miRNAs that regulate its expression.

Results

WB and qRT-PCR showed that STAT6 was obviously up-regulated in synovial tissues of RA patients as well as RA fibroblast-like synoviocytes (RA FLSs). Functionally, down-regulation of STAT6 significantly inhibited the growth of RA FLSs as indicated by EdU and CCK-8 assays. In addition, inhibition of STAT6 remarkably promoted apoptosis of RA FLSs. Besides, silence of STAT6 notably suppressed inflammatory cytokine levels, such as TNF-α, IL-6 and IL-1β. Mechanistically, STAT6 was predicted to be the direct target of and negatively regulated by miR-135a-5p. Moreover, STAT6 was involved in the regulation of miR-135a-5p on cell growth, apoptosis and inflammatory response of RA FLSs.

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