Abstract
Behavior alterations in fibroblast-like synoviocytes (FLS) contribute to a pivotal role in pathogenesis of rheumatoid arthritis (RA). MiRNAs are closely involved in a variety of pathologic conditions. In the present study, we aimed to screen for the aberrant expression of miRNAs in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) to further identify the altered expression of miR-26a-5p in RA-FLS and to investigate the role of miR-26a-5p in RA. The altered expression of miR-26a-5p in RA-FLS was screened by microarray analysis and confirmed by quantitative real time PCR. The effect of miR-26a-5p on proliferation, cell cycle, apoptosis, and invasion in RA-FLS were studied. The verification of miR-26a-5p target mRNA and downstream signaling pathway was elucidated by bioinformatics analysis, dual luciferase reporter assay, and western blot. Expression of miR-26a-5p was higher in RA-FLS than in fibroblast-like synoviocytes from osteoarthritis patients and trauma patients. Overexpression of miR-26a-5p RA-FLS promoted cells proliferation, G1/S transition, cells invasion, and resisted apoptosis in RA-FLS, whereas it led to contrary effects when inhibiting the expression of miR-26a-5p. The 3′UTR of tensin homolog (PTEN) was directly targetted by miR-26a-5p and activation of phosphoinositide 3-kinase (PI3K)/AKT pathway was observed when overexpression of miR-26a-5p. Our study suggested that miR-26a-5p has a complementary role in cells proliferation, invasion, and apoptosis of RA-FLS, which may be attributed to its activation effect on PI3K/AKT signaling pathway via targetting PTEN. MiR-26a-5p is likely to be a clinically helpful target for novel therapeutic strategies in RA.
Highlights
Rheumatoid arthritis (RA) is a common systemic autoimmune disease, characterized by chronic inflammatory of the joints, destruction in cartilage and joint bone, and a series of extra-articular manifestations including rheumatoid nodules, pulmonary interstitial disease, and Felty’s syndrome [1,2]
The expression profiles of miRNAs in fibroblast-like synoviocytes from three RA patients and three knee joint trauma patients were evaluated by miRNA microarray analysis
Results showed that cell proliferation rate was slightly higher in RA-fibroblast-like synoviocytes (FLS) transfected with miR-26a-5p mimic compared with that transfected with mimic negative control (NC) in day 2 (375.30 +− 24.59% vs 349.33 +− 30.42%, P
Summary
Rheumatoid arthritis (RA) is a common systemic autoimmune disease, characterized by chronic inflammatory of the joints, destruction in cartilage and joint bone, and a series of extra-articular manifestations including rheumatoid nodules, pulmonary interstitial disease, and Felty’s syndrome [1,2]. It is believed that miRNAs potentially regulate at least 20–30% of all human protein coding genes [8], which are closely involved in a series of biological process including cell cycle, cellular proliferation, differentiation, apoptosis, and immunoreaction [9,10,11]. Several previous studies have focussed on the role of miRNAs in RA-FLS and revealed that up-regulated or down-regulated certain miRNAs were involved in the alteration of proliferation, invasion, and apoptosis in RA-FLS, indicating that the identification of these miRNAs might contribute to our understanding about the molecular mechanism of RA [16,17,18]
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