Abstract

BackgroundmiR-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.MethodsQuantitative 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.ResultsmiR-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.ConclusionmiR-431-5p regulates cell proliferation, apoptosis, and cell cycle of RA FLSs by targeting XIAP, suggesting its potential in the treatment of RA.

Highlights

  • MiR-431-5p is dysregulated in various cancers and plays an important function in the development of cancer

  • We have demonstrated that miR-431-5p was downregulated in rheumatoid arthritis (RA) Fibroblast-like synoviocyte (FLS) and targeted the X-linked inhibitor of apoptosis protein (XIAP) to regulate cell proliferation, apoptosis, and cell cycle

  • MiR431-5p was reduced in human fibroblast-like synoviocytes (HFLS)-RA cells with TNF-α treatment compared with that without TNF-α treatment (p = 0.001, Fig. 1c), suggesting that dysregulated miR-431-5p might be involved in the development of RA

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Summary

Introduction

MiR-431-5p is dysregulated in various cancers and plays an important function in the development of cancer. Its role in fibroblast-like synoviocytes (FLSs) in patients with rheumatoid arthritis (RA) remains to be understood. Fibroblast-like synoviocytes (FLSs) constitute a major portion of the synovial intima and are pivotal to the development of RA. RA patients possess hyperactivated FLSs that have tumor cell-like properties, including excessive proliferation with repressed apoptosis, migration, invasion, Wang et al Arthritis Research & Therapy (2020) 22:231 and persistent production of various inflammatory cytokines, chemokines, and matrix metalloproteinases [6]. These hallmarks contribute to the thickening of the synovium and formation of pannus, thereby culminating in articular deformity. There are no currently available drugs that target hyperactivated FLSs as treatment for RA

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