MicroRNA-27a Inhibits Cell Migration and Invasion of Fibroblast-Like Synoviocytes by Targeting Follistatin-Like Protein 1 in Rheumatoid Arthritis

Mol Cells. 2016 Aug 31;39(8):611-8. doi: 10.14348/molcells.2016.0103. Epub 2016 Aug 8.


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 NFκB 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/NFκB pathway.

Keywords: fibroblast-like synoviocyte; follistatin-like protein 1; microRNA; rheumatoid arthritis.

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / therapy*
  • Cell Movement / genetics
  • Cells, Cultured
  • Female
  • Fibroblasts / physiology*
  • Follistatin-Related Proteins / genetics
  • Follistatin-Related Proteins / metabolism*
  • Genetic Therapy
  • Humans
  • Male
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • MicroRNAs / genetics*
  • Middle Aged
  • NF-kappa B / metabolism
  • Synovial Membrane / pathology*
  • Toll-Like Receptor 4 / metabolism
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism


  • Follistatin-Related Proteins
  • MIRN27 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Matrix Metalloproteinases
  • rho GTP-Binding Proteins