Down-regulation of microRNA-142-3p inhibits the aggressive phenotypes of rheumatoid arthritis fibroblast-like synoviocytes through inhibiting nuclear factor-κB signaling.

Jianhong Qiang,Xichao Yang,Zhenbiao Wu,Tingting Lv

doi:10.1042/bsr20190700

Jianhong Qiang, Xichao Yang + Show 2 more

Open Access

https://doi.org/10.1042/bsr20190700

Copy DOI

Abstract

The present study aimed to investigate the regulatory roles of miR-142-3p on the aggressive phenotypes of rheumatoid arthritis (RA) human fibroblast-like synoviocytes (RA-HFLSs), and reveal the potential mechanisms relating with nuclear factor-κB (NF-κB) signaling. miR-142-3p expression was detected in RA synovial tissues and RA-HFLSs by quantitative real-time PCR (qRT-PCR) and Northern blot analysis. RA-HFLSs were transfected with miR-142-3p inhibitor and/or treated with 10 µg/l tumor necrosis factor α (TNF-α). The viability, colony formation, apoptosis, migration, invasion, and the levels of interleukin (IL)-6, and matrix metalloproteinase 3 (MMP-3) were detected. The mRNA expressions of B-cell lymphoma-2 (Bcl-2), Bax, Bad, IL-6, and MMP-3 were detected by qRT-PCR. Moreover, the expression of Bcl-2, IL-1 receptor-associated kinase 1 (IRAK1), Toll-like receptor 4 (TLR4), NF-κB p65, and phosphorylated NF-κB p65 (p-NF-κB p65) were detected by Western blot. The interaction between IRAK1 and miR-142-3p was identified by dual luciferase reporter gene assay. MiR-142-3p was up-regulated in RA synovial tissues and RA-HFLSs. TNF-α activated the aggressive phenotypes of RA-HFLSs, including enhanced proliferation, migration, invasion, and inflammation, and inhibited apoptosis. miR-142-3p inhibitor significantly decreased the cell viability, the number of cell clones, the migration rate, the number of invasive cells, the contents and expression of IL-6 and MMP-3, and increased the apoptosis rate and the expressions of Bax and Bad, and decreased Bcl-2 expression of TNF-α-treated RA-HFLSs. MiR-142-3p inhibitor significantly reversed TNF-α-induced up-regulation of IRAK1, TLR4, and p-NF-κB p65 in TNF-α-treated RA-HFLSs. Besides, IRAK1 was a target of miR-142-3p. The down-regulation of miR-142-3p inhibited the aggressive phenotypes of RA-HFLSs through inhibiting NF-κB signaling.

Highlights

Rheumatoid arthritis (RA) is a common autoimmune disease that affects 0.5–1% of the population worldwide [1]
The expression of miR-142-3p was detected in both RA tissues and rheumatoid arthritis human fibroblast-like synoviocyte (RA-HFLS). quantitative real-time PCR (qRT-PCR) showed that the expression of miR-142-3p in synovial tissues was significantly higher in RA patients than in OA patients, and was significantly higher in RA patients at stage IV than in those at stage III (P
We found that the transfection of miR-142-3p inhibitor significantly decreased the cell viability, the number of cell clones, the migration rate, the number of invasive cells, and the expression of B-cell lymphoma-2 (Bcl-2) expression, and increased the expressions of Bax and Bad, and the apoptosis rate of tumor necrosis factor α (TNF-α)-treated RA-HFLSs

Summary

Introduction

Rheumatoid arthritis (RA) is a common autoimmune disease that affects 0.5–1% of the population worldwide [1]. RA is characterized by chronic inflammation in synovial tissues, and accompanied with the symptoms of pain, swelling, and stiffness of the joints [2]. Since RA contributes the destruction of cartilage and bone, RA is considered as one of the most common causes of disability [3]. The therapeutic strategies for RA mainly focus on the control of pain and inflammation, as well as the protection of joint damage [4]. With the increasing revelation of the molecular mechanisms involved in the pathogenesis of RA, molecular targeting therapy has become a promising therapeutic strategy for RA

Methods

Results

Conclusion