Circ_AFF2 facilitates proliferation and inflammatory response of fibroblast-like synoviocytes in rheumatoid arthritis via the miR-375/TAB2 axis.

Abstract

Circular RNAs (circRNAs) have been implicated in the pathological regulation of human diseases by acting as microRNA (miRNA) sponges to affect gene expression. CircRNA Fragile Mental Retardation 2 (circ_AFF2) was dysregulated in rheumatoid arthritis (RA), but little is known about its specific function and hidden molecular mechanism in RA. Circ_AFF2, miR-375 and TAK1-binding 2 (TAB2) expression levels were determined through the quantitative real-time polymerase chain reaction (qRT-PCR). Flow cytometry was performed to analyze cell cycle and apoptosis. Cell proliferation detection was conducted by 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The protein levels were measured using western blot. Inflammatory response was evaluated by enzyme-linked immunosorbent assay (ELISA). RNA pull-down assay was used to select the miRNA target of circ_AFF2. The interaction between miR-375 and circ_AFF2 or TAB2 was analyzed using the dual-luciferase reporter assay. Contrasted to normal samples and fibroblast-like synoviocytes (FLS), circ_AFF2 expression was upregulated in RA blood samples and FLS-RA cells. Cell cycle, proliferation and inflammatory response were blocked while apoptosis was promoted in FLS-RA after the downregulation of circ_AFF2. In addition, circ_AFF2 could interact with miR-375 and the function of circ_AFF2 was achieved by sponging miR-375 in FLS-RA cells. Moreover, TAB2 was a target of miR-375 and miR-375 repressed RA progression by decreasing TAB2 expression in FLS-RA cells. More importantly, circ_AFF2 promoted the expression of TAB2 by targeting miR-375. These findings clarified that circ_AFF2 induced cell progression, inflammatory response in FLS-RA cells via the miR-375/TAB2 axis. Circ_AFF2 could be used as a biomarker in the diagnosis and treatment of RA.

• Authors: Liqiang Zhi, Jingqi Liang, Wei Huang, Jianbing Ma, Zhong Qing, Xi Wang
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 119 Pg. 104617 (04 2021) ISSN: 1096-0945 [Electronic] Netherlands
• PMID: 33535081 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Adaptor Proteins, Signal Transducing
• MIRN375 microRNA, human
• MicroRNAs
• RNA, Circular
• TAB2 protein, human

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Apoptosis (genetics)
• Arthritis, Rheumatoid (blood, genetics, pathology)
• Base Sequence
• Cell Cycle (genetics)
• Cell Line
• Cell Proliferation (genetics)
• Disease Progression
• Down-Regulation (genetics)
• Fibroblasts (pathology)
• Humans
• Inflammation (genetics, pathology)
• MicroRNAs (genetics, metabolism)
• RNA, Circular (blood, genetics, metabolism)
• Signal Transduction
• Synoviocytes (pathology)
• Up-Regulation (genetics)