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2016 ; 39
(8
): 611-8
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MicroRNA-27a Inhibits Cell Migration and Invasion of Fibroblast-Like Synoviocytes
by Targeting Follistatin-Like Protein 1 in Rheumatoid Arthritis
#MMPMID27498552
Shi DL
; Shi GR
; Xie J
; Du XZ
; Yang H
Mol Cells
2016[Aug]; 39
(8
): 611-8
PMID27498552
show ga
Fibroblast-like synoviocytes (FLS) with aberrant expression of microRNA (miRNA)
are critical pathogenic regulators in rheumatoid arthritis (RA). Previous studies
have found that overexpression or silencing of miRNA can contribute to the
development of miRNA-based therapeutics in arthritis models. In this study, we
explored the effects of miR-27a on cell migration and invasion in cultured FLS
from RA patients. We found that miR-27a was markedly downregulated in the serum,
synovial tissue, and FLS of RA patients. Meanwhile, the expression of
follistatin-like protein 1 (FSTL1) was upregulated, which suggests that FSTL1
plays a key role in RA development. The results of a Transwell assay showed that
miR-27a inhibited FLS migration and invasion. However, miR-27a inhibition
promoted the migration and invasion of FLS. In addition, the down-regulated
expression of matrix metalloproteinases (MMP2, MMP9, and MMP13) and Rho family
proteins (Rac1, Cdc42, and RhoA) was detected after treatment with miR-27a in
RA-FLS by quantitative reverse transcription-PCR and western blot analysis. Then,
a luciferase reporter assay validated that miR-27a targeted the 3-untranslated
region (3'-UTR) of FSTL1. Moreover, miR-27a caused a significant decrease of
FSTL1. In addition, the expression of TLR4 and NF?B was inhibited by miR-27a but
increased by FSTL1 overexpression. In conclusion, we found that miR-27a inhibited
cell migration and invasion of RA-FLS by targeting FSTL1 and restraining the
TLR4/NF?B pathway.