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MicroRNA‑34a‑3p inhibits proliferation of rheumatoid arthritis fibroblast‑like synoviocytes.

Abstract：

:Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterized by synovial inflammation. Fibroblast‑like synoviocytes (FLS) serve a vital role in the initiation and perpetuation of the immune response in patients with RA. The present study aimed to investigate the potential role of microRNA (miR)‑34a‑3p in the pathogenesis of RA. FLS were collected from patients with RA and osteoarthritis (OA). The miR‑34a‑3p mimics and inhibitor vectors were constructed and transfected into RAFLS using Lipofectamine® 2000. Cell proliferation was determined by Cell Counting kit‑8 assay and cell cycle progression was analyzed by flow cytometry. In addition, the expression levels of cell cycle control genes, matrix metalloproteinase (MMP)‑1 and MMP‑9, and pro‑inflammatory cytokines were detected by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The potential targets of miR‑34a‑3p were predicted by TargetScan and MiRWalk; the target genes were further verified using a luciferase reporter assay. The expression levels of miR‑34a‑3p were generally lower in RAFLS compared with in OAFLS. miR‑34a‑3p overexpression significantly inhibited the proliferation of FLS (P<0.01) by suppressing the expression levels of cyclin‑dependent kinase 2, cell division cycle 25A and cyclin D1 (P<0.01), and arresting FLS cell cycle progression at the G1 phase. Furthermore, the expression levels of MMP‑1 and 9 were markedly decreased, as were the mRNA and protein expression levels of pro‑inflammatory cytokines (tumor necrosis factor α and interleukin 6; P<0.01). Murine double minute 4 (MDM4) was predicted and verified as a potential target gene of miR‑34a‑3p; the 547‑554 nt position of the MDM4 3'‑untranslated region harbored one potential binding site for miR‑204‑3p. The results of the present study indicated that miR‑34a‑3p may be considered a promising therapeutic target for RA through inhibiting FLS proliferation and suppressing the production of pro‑inflammatory cytokines and MMPs.

journal_name

Mol Med Rep

journal_title

Molecular medicine reports

authors

Hou C,Wang D,Zhang L

doi

10.3892/mmr.2019.10516

subject

Has Abstract

pub_date

2019-09-01 00:00:00

pages

2563-2570

issue

eissn

1791-2997

issn

1791-3004

journal_volume

pub_type

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MicroRNA‑34a‑3p inhibits proliferation of rheumatoid arthritis fibroblast‑like synoviocytes.