MicroRNA-126 affects rheumatoid arthritis synovial fibroblast proliferation and apoptosis by targeting PIK3R2 and regulating PI3K-AKT signal pathway

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and destruction of the joints as well as an increased risk of cardiovascular disease. RA synovial fibroblasts (RASFs) are involved in the progression of RA and release pro-inflammatory cytokines. On the other hand, microRNAs (miRs) may help control the inflammatory response of immune and non-immune cells. Therefore, our study used lentiviral expression vectors to test the effects of miR-126 overexpression on RASF proliferation and apoptosis. Luciferase experiments verified the targeting relationship between miR-126 and PIK3R2 gene. The co-transfection of anti-miR-126 and PIK3R2 siRNA to RASFs were used to identify whether PIK3R2 was directly involved in proliferation and apoptosis of miR-126-induced RASFs. Real-time polymerase chain reaction (PCR) was used to detect miR-126 and PIK3R2 expressions. MTT assay was used to detect cell proliferation. Flow cytometry was used to detect cell apoptosis and cell cycle. Western blotting was used to detect PIK3R2, PI3K, AKT and p-AKT proteins. After Lv-miR-126 infected RASFs, the relative expression of miR-126 was significantly enhanced. MiR-126 promoted RASF proliferation and inhibited apoptosis. Levels of PIK3R2 decreased while total PI3K and p-AKT levels increased in RASFs overexpressing miR-126. Co-transfection of anti-miR-126 and PIK3R2 siRNA also increased PI3K and p-AKT levels as well as RASF proliferation and reduced apoptosis, as compared to anti-miR-126 treatment alone. Finally, luciferase reporter assays showed that miR-126 targeted PIK3R2. Our data indicate that miR-126 overexpression in RASFs inhibits PIK3R2 expression and promotes proliferation while inhibiting apoptosis. This suggests inhibiting miR-126 may yield therapeutic benefits in the treatment of RA.

MiR‐126 correlates with increased disease severity and promotes keratinocytes proliferation and inflammation while suppresses cells' apoptosis in psoriasis

“…In addition, TNF‐α, IFN‐γ, IL‐17A and IL‐22 levels were elevated while IL‐10 level was lowered in miR‐126 mimic group compared with NC mimic group. Here are several possible explanations for our results: (i) according to previous studies, the overexpression of miR‐126 could promote cells' proliferation and inhibits cells' apoptosis by regulating multiple pathways; (ii) and miR‐126 also upregulates the expression of pro‐inflammatory cytokines by modulating immune‐related factors such as Dnmt1 and NF‐κB . These results in our study indicated that miR‐126 could be served as a potential treatment target in psoriasis patients.…”

“…MiR‐126 is a member of miRNAs that are reported to be involved in the development and progression of several autoimmune diseases such as RA and SLE . A study elucidates that miR‐126 expression is increased in the CD4+ T cells of SLE patients and promotes the progression of SLE by enhancing T‐cell autoreactivity through directly targeting DNA methyltransferase 1 (Dnmt1) .…”

“…Accumulating studies disclose that dysregulation of miRNAs including miR‐31, miR‐155, and miR‐26b is involved in the pathological processes of a variety of immune diseases including psoriasis . MiR‐126, located on human chromosome 9q34.3, has been reported to participate in the development and progression of multiple immune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD) . However, to the best of our knowledge, the role of miR‐126 in the etiology of psoriasis has not been reported.…”

“…[13][14][15] MiR-126, located on human chromosome 9q34.3, has been reported to participate in the development and progression of multiple immune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD). [16][17][18] However, to the best of our knowledge, the role of miR-126 in the etiology of psoriasis has not been reported. Therefore, this study aimed to investigate the miR-126 expression of lesional skin and its correlation with clinical features in psoriasis patients and to explore the effect of upregulation of miR-126 on cells' proliferation, apoptosis, and inflammation in human keratinocytes.…”

Retracted: miR‐145 eliminates lipopolysaccharides‐induced inflammatory injury in human fibroblast‐like synoviocyte MH7A cells

“…[29][30][31][32] LPS increases the secretion of pro-inflammatory cytokines in fibroblast-like synoviocytes, which leads to the activation of the PI3K/ AKT and MAPK/mTOR pathways, thereby inducing apoptotic and inflammatory injury in these cells. [29][30][31][32] LPS increases the secretion of pro-inflammatory cytokines in fibroblast-like synoviocytes, which leads to the activation of the PI3K/ AKT and MAPK/mTOR pathways, thereby inducing apoptotic and inflammatory injury in these cells.…”