MicroRNA-126 affects rheumatoid arthritis synovial fibroblast proliferation and apoptosis by targeting PIK3R2 and regulating PI3K-AKT signal pathway
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Yuan Qu1,2,*, Jing Wu2,3,*, Jia-Xin Deng2, Yu-Ping Zhang2, Wan-Yi Liang2, Zhen-Lan Jiang2, Qing-Hong Yu2, Juan Li1,3
1Department of Internal Medicine of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510510, Guangdong, P. R. China
2Department of Rheumatology and Clinical Immunology, Zhujiang Hospital of Southern Medical University, Guangzhou 510282, Guangdong, P. R. China
3Department of Rheumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510510, Guangdong, P. R. China
*These authors have contributed equally to this work
Juan Li, email: [email protected]
Qing-Hong Yu, email: [email protected]
Keywords: microRNA-126, PIK3R2, PI3K-AKT, rheumatoid arthritis, synovial fibroblasts
Received: April 14, 2016 Accepted: July 10, 2016 Published: October 06, 2016
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.
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