Circ_0001947 promotes cell proliferation, invasion, migration and inflammation and inhibits apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes through miR-671-5p/STAT3 axis

Yang Yang,Shudian Lin,Feng Zhan,Zhou Yang,Yanyan Huang

doi:10.1186/s13018-022-02939-3

Abstract

BackgroundCircular RNAs (circRNAs) have emerged as vital regulators in the development of rheumatoid arthritis (RA). In this study, we aimed to explore the functions and mechanisms of circ_0001947 in RA.MethodsThe expression of circ_0001947, microRNA-671-5p (miR-671-5p) and signal transducer and activator of transcription 3 (STAT3) was determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell Counting Kit-8 (CCK-8) assay, 5′-ethynyl-2′-deoxyuridine (EdU) assay, flow cytometry analysis, transwell assay and wound-healing assay were performed to assess cell proliferation, apoptosis, invasion and migration. The concentrations of inflammatory factors were examined with enzyme-linked immunosorbent assay (ELISA) kits. Dual-luciferase reporter assay was used to analyze the relationships of circ_0001947, miR-671-5p and STAT3.ResultsCirc_0001947 was upregulated in RA patients and RA-FLSs. Knockdown of circ_0001947 repressed cell proliferation, invasion, migration and inflammatory response and facilitated apoptosis in RA-FLSs. Circ_0001947 served as the sponge for miR-671-5p and the inhibitory effect of circ_0001947 in RA-FLS progression was reversed by miR-671-5p inhibition. STAT3 was the target gene of miR-671-5p. MiR-671-5p overexpression restrained RA-FLS growth, invasion, migration and inflammation and promoted apoptosis, but STAT3 upregulation reversed the impacts.ConclusionCirc_0001947 contributed to the progression of RA-FLSs by elevating STAT3 through adsorbing miR-671-5p.

Highlights

Rheumatoid arthritis (RA) is a chronic autoimmune disease and featured by the progressive damage to cartilage and bone, imposing a huge burden on patients and society [1, 9, 27]
The results were identified by quantitative real-time polymerase chain reaction (qRT-PCR), which showed that si-circ_0001947 transfection decreased circ_0001947 expression in rheumatoid arthritis (RA)-fibroblast-like synovial cells (FLSs) compared to si-NC control group (Fig. 2A)
Circ_0001947 knockdown decreased the concentrations of TNF-α and IL-1β in RA-FLSs (Fig. 2H). These findings suggested that circ_0001947 knockdown inhibited the progression of RA-FLSs

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease and featured by the progressive damage to cartilage and bone, imposing a huge burden on patients and society [1, 9, 27]. As the key cells related to synovial tissue formation, fibroblast-like synovial cells (FLSs) are involved in the inflammatory response of synovial joints, leading to cartilage destruction and RA [14]. RA-FLSs have been reported to have the similar properties to tumor cells, such as proliferation, invasion, migration, and anti-apoptosis [3, 25]. Results: Circ_0001947 was upregulated in RA patients and RA-FLSs. Knockdown of circ_0001947 repressed cell proliferation, invasion, migration and inflammatory response and facilitated apoptosis in RA-FLSs. Circ_0001947 served as the sponge for miR-671-5p and the inhibitory effect of circ_0001947 in RA-FLS progression was reversed by miR671-5p inhibition. MiR-671-5p overexpression restrained RA-FLS growth, invasion, migration and inflammation and promoted apoptosis, but STAT3 upregulation reversed the impacts. Conclusion: Circ_0001947 contributed to the progression of RA-FLSs by elevating STAT3 through adsorbing miR-671-5p

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Conclusion