Lnc RNA ZFAS1 regulates the proliferation, apoptosis, inflammatory response and autophagy of fibroblast-like synoviocytes via miR-2682-5p/ADAMTS9 axis in rheumatoid arthritis.

Publisher: Portland Press on behalf of the Biochemical Society Country of Publication: England NLM ID: 8102797 Publication Model: Print Cited Medium: Internet ISSN: 1573-4935 (Electronic) Linking ISSN: 01448463 NLM ISO Abbreviation: Biosci Rep Subsets: MEDLINE

Publication: London : Portland Press on behalf of the Biochemical Society
Original Publication: London : The Biochemical Society, c1981-

Apoptosis* ; Autophagy* ; Cell Proliferation*; ADAMTS9 Protein/*metabolism ; Arthritis, Rheumatoid/*enzymology ; Knee Joint/*enzymology ; MicroRNAs/*metabolism ; RNA, Long Noncoding/*metabolism ; Synoviocytes/*enzymology; ADAMTS9 Protein/genetics ; Apoptosis Regulatory Proteins/metabolism ; Arthritis, Rheumatoid/genetics ; Arthritis, Rheumatoid/pathology ; Autophagy-Related Proteins/metabolism ; Case-Control Studies ; Cells, Cultured ; Cytokines/metabolism ; Gene Expression Regulation ; Humans ; Knee Joint/pathology ; MicroRNAs/genetics ; RNA, Long Noncoding/genetics ; Signal Transduction ; Synoviocytes/pathology

Backgrounds: Rheumatoid arthritis (RA) is a frequent autoimmune disease. Emerging evidence indicated that ZNFX1 antisense RNA1 (ZFAS1) participates in the physiological and pathological processes in RA. However, knowledge of ZFAS1 in RA is limited, the potential work pathway of ZFAS1 needs to be further investigated.
Methods: Levels of ZFAS1, microRNA (miR)-2682-5p, and ADAM metallopeptidase with thrombospondin type 1 motif 9 (ADAMTS9) were estimated using quantitative real-time polymerase chain reaction (qRT-PCR) assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was conducted to explore the ability of cell proliferation in fibroblast-like synoviocytes (FLS-RA). Cell apoptosis was measured via flow cytometry. Also, levels of ADAMTS9, apoptosis-related proteins, cleaved-caspase-3 (active large subunit), and autophagy-related proteins were identified adopting Western blot. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the productions of inflammatory cytokines. Beside, the interrelation between miR-2682-5p and ZFAS1 or ADAMTS9 was verified utilizing dual-luciferase reporter assay.
Results: High levels of ZFAS1 and ADAMTS9, and a low level of miR-2682-5p were observed in RA synovial tissues and FLS-RA. Knockdown of ZFAS1 led to the curbs of cell proliferation, inflammation, autophagy, and boost apoptosis in FLS-RA, while these effects were abolished via regaining miR-2682-5p inhibition. Additionally, the influence of miR-2682-5p on cell phenotypes and inflammatory response were eliminated by ADAMTS9 up-regulation in FLS-RA. Mechanically, ZFAS1 exerted its role through miR-2682-5p/ADAMTS9 axis in RA.
Conclusion: ZFAS1/miR-2682-5p/ADAMTS9 axis could modulate the cell behaviors, inflammatory response in FLS-RA, might provide a potential therapeutic target for RA treatment.
(© 2020 The Author(s).)

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Keywords: Rheumatoid arthritis; cell autophagy; inflammatory

0 (Apoptosis Regulatory Proteins)
0 (Autophagy-Related Proteins)
0 (Cytokines)
0 (MIRN-2682 microRNA, human)
0 (MicroRNAs)
0 (RNA, Long Noncoding)
0 (ZFAS1 long non-coding RNA, human)
EC 3.4.24.- (ADAMTS9 Protein)
EC 3.4.24.- (ADAMTS9 protein, human)

Date Created: 20200804 Date Completed: 20210329 Latest Revision: 20210329

20231215

PMC7435024

10.1042/BSR20201273

32744323