miR-431-5p regulates cell proliferation and apoptosis in fibroblast-like synoviocytes in rheumatoid arthritis by targeti
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RESEARCH ARTICLE
Open Access
miR-431-5p regulates cell proliferation and apoptosis in fibroblast-like synoviocytes in rheumatoid arthritis by targeting XIAP Yuejiao Wang1, Kailin Zhang2, Xiaowei Yuan3, Neili Xu1, Shuai Zhao1, Linxin Hou1, Lili Yang1 and Ning Zhang1*
Abstract Background: miR-431-5p is dysregulated in various cancers and plays an important function in the development of cancer. However, its role in fibroblast-like synoviocytes (FLSs) in patients with rheumatoid arthritis (RA) remains to be understood. Methods: Quantitative real-time polymerase chain reaction was used to detect the relative expression of miR-431-5p in synovial tissues and FLSs. Cell proliferation assays helped examine RA FLS proliferation. Flow cytometry was performed to determine apoptosis and cell cycle progression in RA FLSs. We used dual-luciferase assays to determine the correlation between miR-431-5p and its putative target, X-linked inhibitor of apoptosis (XIAP). Quantitative real-time PCR and western blotting were used to measure XIAP levels in synovial tissues and transfected RA FLSs. Results: miR-431-5p was downregulated in synovial tissues and FLSs of patients with RA. Upregulation of miR-431-5p prohibited cell proliferation and the G0/G1-to-S phase transition but promoted apoptosis in RA FLSs, while miR-431-5p inhibition showed the opposite results. miR-431-5p directly targeted XIAP in RA FLSs and reversely correlated with XIAP levels in synovial tissues. Notably, XIAP silencing partially restored the effects of miR-431-5p inhibition in RA FLSs. Conclusion: miR-431-5p regulates cell proliferation, apoptosis, and cell cycle of RA FLSs by targeting XIAP, suggesting its potential in the treatment of RA. Keywords: Rheumatoid arthritis, Synoviocytes, miR-431-5p, XIAP, Proliferation, Apoptosis
Background Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease with a global prevalence of 0.5–1.0% [1]. Patients with RA may develop clinical hallmarks of joint swelling, arthralgia, and stiffness in the morning; without medical intervention, these symptoms aggravate as disease progresses [2]. Although there has been significant advancement in the treatment regimens for RA, patients continue to experience progressive articular damage with time (detectable in radiographs) and have high rates of articular * Correspondence: [email protected] 1 Department of Rheumatology and Immunology at Shengjing Hospital of China Medical University, Shenyang, Liaoning, China Full list of author information is available at the end of the article
deformity and other complications such as interstitial lung disease and cardiovascular diseases [3, 4]. Therefore, it is imperative to gain a comprehensive understanding of the pathogenesis of RA to develop effective preventive and therapeutic strategies. Fibroblast-like synoviocytes (FLSs) constitute a major portion of the synovial intima and are pivotal to the development of RA. A healthy synovium is comprised of a superficial synovial lining named intima and a deeper zone called sub-lini
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