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

Jiajia Liu; Jianhua Xue; Bo Xu; Junbo Yu; Yuxuan Zhang; Lili Qin; Aixian Zhang; Yang Yang

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

Am J Transl Res. 2022 May 15;14(5):3092-3103. eCollection 2022.

Authors

Jiajia Liu¹, Jianhua Xue¹, Bo Xu², Junbo Yu¹, Yuxuan Zhang³, Lili Qin⁴, Aixian Zhang⁵, Yang Yang¹

Affiliations

¹ Department of Trauma Center, Affiliated Hospital of Nantong University Nantong, Jiangsu Province, China.
² Department of Orthopedics, Qidong Hospital of Traditional Chinese Medicine Nantong, Jiangsu Province, China.
³ Department of Foot and Ankle Surgery, Wuxi No. 9 People's Hospital Affiliated to Soochow University Wuxi, Jiangsu Province, China.
⁴ Department of Endoscopic Center, Affiliated Hospital of Nantong University Nantong, Jiangsu Province, China.
⁵ Department of General Practice Medicine, Affiliated Hospital of Nantong University Nantong, Jiangsu Province, China.

PMID: 35702088
PMCID: PMC9185078

Abstract

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.

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.

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.

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

Keywords: Fibroblast-like synoviocytes; apoptosis; microrna-135a-5p; proliferation; rheumatoid arthritis; signal transducers and activators of transcription 6.