ZFAS1 knockdown inhibits ﬁbroblast‑like synoviocyte proliferation, migration, invasion and inflammation, and promotes apoptosis via miR‑3926/FSTL1 in rheumatoid arthritis

Wang,Qiang; Chu,Peigang; Yu,Xia; Li,Jun; Zhang,Wenzheng; Gong,Mingzhi

doi:10.3892/etm.2021.10346

ZFAS1 knockdown inhibits ﬁbroblast‑like synoviocyte proliferation, migration, invasion and inflammation, and promotes apoptosis via miR‑3926/FSTL1 in rheumatoid arthritis

Authors:
- Qiang Wang
- Peigang Chu
- Xia Yu
- Jun Li
- Wenzheng Zhang
- Mingzhi Gong
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Affiliations: Department of Traumatic Orthopaedics, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China, Department of Joint Sports Medicine, Taian City Central Hospital, Taian, Shandong 271000, P.R. China, Department of Nuclear Medicine, Taian City Central Hospital, Taian, Shandong 271000, P.R. China
Published online on: June 29, 2021 https://doi.org/10.3892/etm.2021.10346
Article Number: 914

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Abstract

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by joint disorders. Long non‑coding RNA zinc finger antisense 1 (ZFAS1) is aberrantly expressed in numerous human diseases, including RA. The present study aimed to investigate the functions and underlying mechanisms of ZFAS1 in RA. Reverse transcription‑quantitative PCR was performed to determine the expression levels of ZFAS1, microRNA (miR)‑3926 and follistatin‑like protein 1 (FSTL1). MTT assay, flow cytometric analysis and Transwell assay were performed to examine the proliferation, apoptosis, migration and invasion of ﬁbroblast‑like synoviocytes (FLSs), respectively. Western blotting was employed to measure the protein expression levels of cleaved caspase‑3, interleukin (IL)‑6, IL‑1β, tumor necrosis factor‑α and FSTL1. Dual‑luciferase reporter assay was performed to verify the interaction between miR‑3926 and ZFAS1 or FSTL1. The results demonstrated that ZFAS1 and FSTL1 were upregulated, and miR‑3926 was downregulated in RA synovial tissues and RA‑FLSs. ZFAS1 knockdown suppressed cell proliferation, migration, invasion and inflammatory cytokine production, and induced apoptosis in RA‑FLSs. ZFAS1 acted as a sponge for miR‑3926, and ZFAS1 overexpression abolished the impact of miR‑3926 on the development of RA‑FLSs. FSTL1 was a direct target of miR‑3926, and the effect of FSTL1 knockdown on the progression of RA‑FLSs was rescued by miR‑3926 inhibition. Furthermore, ZFAS1 regulated FSTL1 expression levels via sponging miR‑3926 in RA‑FLSs. In conclusion, ZFAS1 knockdown inhibited RA‑FLS proliferation, migration, invasion and inflammatory cytokine production, and induced apoptosis in RA via the miR‑3926/FSTL1 axis.

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