MicroRNA-133 suppresses cell viability and migration of rheumatoid arthritis fibroblast-like synoviocytes by down-regulation of MET, EGFR, and FSCN1 expression

Mol Cell Biochem. 2022 Nov;477(11):2529-2537. doi: 10.1007/s11010-022-04457-6. Epub 2022 May 20.

Abstract

Aberrant proliferation and migration of fibroblast-like synoviocytes (FLS) are major characteristics of rheumatoid arthritis (RA). MicroRNA-133 (miR-133) is a tumor-suppressive miRNA that targets various genes responsive for cell proliferation and migration. The aim of this study was to examine the effect of miR-133 on RA FLS. A high throughput miRNA microarray was performed in synovium from mice with collagen-induced arthritis (CIA). Expression levels of miR-133 and the putative targets were determined in synovium and FLS from patients with RA and mice with CIA. Overexpression of miR-133 in RA FLS was performed by lentiviral vector-mediated transfer of precursor miRNA (pre-miR). The expression of miR-133a/b was decreased in the joint tissue and FLS of CIA mice, as determined by miRNA array and qRT-PCR. Down-regulation of miR-133a/b expression could also be observed in synovium and FLS from patients with RA. Overexpression of miR-133 reduced cell viability and migration of RA FLS, with decreased levels of FSCN1, EGFR, and MET. Our findings demonstrated the inhibitory effects of miR-133 on FLS viability and migration, and might contribute to the pharmacologic development of miR-133 therapeutics in patients with RA.

Keywords: Collagen-induced arthritis; Fibroblast-like synoviocytes; MicroRNA-133; Rheumatoid arthritis.

MeSH terms

  • Animals
  • Arthritis, Experimental* / metabolism
  • Arthritis, Rheumatoid* / genetics
  • Arthritis, Rheumatoid* / metabolism
  • Carrier Proteins / metabolism
  • Cell Proliferation / genetics
  • Cell Survival
  • Cells, Cultured
  • Down-Regulation
  • ErbB Receptors / metabolism
  • Fibroblasts / metabolism
  • Mice
  • MicroRNAs* / metabolism
  • Microfilament Proteins / metabolism
  • Proto-Oncogene Proteins c-met / metabolism
  • Synoviocytes* / metabolism

Substances

  • ErbB Receptors
  • MicroRNAs
  • Mirn133 microRNA, mouse
  • Microfilament Proteins
  • Carrier Proteins
  • Proto-Oncogene Proteins c-met