MicroRNA-4423-3p inhibits proliferation of fibroblast-like synoviocytes by targeting matrix metalloproteinase 13 in rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that is increasing in incidence worldwide. RA is regulated by a variety of microRNAs (miRNAs/miR). Moreover, analysis of public data has revealed that miR-4423-3p is significantly downregulated in peripheral blood mononuclear cells of RA patients. This study investigated the role of miR-4423-3p in RA. The levels of miR-4423-3p and matrix metalloproteinase 13 (MMP13) in RA patients and the regulatory relationship between miR-4423-3p and MMP13 were analyzed using public data. A dual-luciferase reporter assay was performed to verify that miR-4423-3p targets MMP13 in human fibroblast-like synoviocyte (HFLS) RA cells (HFLS-RA). Following the overexpression of miR-4423-3p, miR-4423-3p inhibitor, and MMP13 in HFLS-RA, viability, proliferation, cell cycle, apoptosis, and invasion/migration assays were used to detect the effects of miR-4423-3p targeting MMP13 on cell biological processes. The results revealed that miR-4423-3p was downregulated in peripheral blood mononuclear cells of RA patients and MMP13 was upregulated in synovial tissue of RA patients. miR-4423-3p targets the 3ʹ untranslated region of MMP13 and downregulates MMP13 expression. After overexpression of miR-4423-3p, cell proliferation, migration, and invasion were inhibited, the cell cycle was prevented and cell apoptosis was promoted. Overexpression of MMP13 promoted cell proliferation, migration, and invasion, while accelerating the cell cycle process and suppressing apoptosis. The findings indicate that in HFLS-RA cells, overexpression of miR-4423-3p inhibited proliferation, migration, and invasion, and promoted apoptosis by negatively regulating MMP13. The overexpression of miR-4423-3p might be a novel strategy for the treatment of RA.

Current situation and trend of non-coding RNA in rheumatoid arthritis: a review and bibliometric analysis

“…MiRNAs can bind to complementary base sequences on target mRNA molecules, resulting in decreased stability, degradation, or inhibition of the translation process of the target mRNA, ultimately reducing the expression level of the target protein ( 162 ). For example, miR-4423-3p inhibits the proliferation, migration and invasion of RA-FLS by downregulating the expression level of MMP13 ( 163 ); MiR-449a downregulates the expression of High Mobility Group Box 1 (HMGB1) to inhibit the proliferation, migration, and invasion of RA-FLS ( 164 ); MicroRNA-133 downregulates mesenchymal-epithelial transition factor (MET), Epidermal Growth Factor Receptor (EGFR), and Fascin Actin-Bundling Protein 1 (FSCN1) to suppress the proliferation, migration, and invasion of RA-FLS ( 165 ).…”

Plumbagin relieves rheumatoid arthritis through nuclear factor kappa-B (NF-κB) pathway

“…MMP-1 and MMP-13 are also important participants in RA cartilage injury [ 26 , 28 ]. It has been reported that miR-4423-3p inhibits the proliferation of HFLS-RAs by targeting MMP-13 [ 29 ]. Here, owing to the notable inhibitory effects on the expressions of MMP-1, MMP-3 and MMP-13 in IL-1β-induced HFLS-RAs, the treatment of plumbagin was proved to significantly attenuate the RA-induced tissue damage.…”