LncNFYB promotes the proliferation of rheumatoid arthritis fibroblast-like synoviocytes via LncNFYB/ANXA2/ERK1/2 axis

J Biol Chem. 2024 Feb;300(2):105591. doi: 10.1016/j.jbc.2023.105591. Epub 2023 Dec 21.

Abstract

Long noncoding RNAs (lncRNAs) are specifically expressed in different diseases and regulate disease progression. To explore the functions of rheumatoid arthritis (RA)-specific lncRNA, we determined the lncRNA expression profile of fibroblast-like synoviocytes (FLS) obtained from patients with RA and osteoarthritis (OA) using a LncRNA microarray and identified up-regulated LncNFYB in RA as a potential therapeutic target. Using gain- and loss-of-function studies, LncNFYB was proven to promote FLS proliferation and cell cycle progress but not affect their invasion, migration, and apoptotic abilities. Further investigation discovered that LncRNA could combine with annexin A2 (ANXA2) and enhance the level of phospho-ANXA2 (Tyr24) in the plasma membrane area, which induced the activation of ERK1/2 to promote proliferation. These findings provide new insights into the biological functions of LncNFYB on modification of FLS, which may be exploited for the therapy of RA.

Keywords: ANXA2; ERK1/2; fibroblast-like synoviocytes; lncRNA; rheumatoid arthritis.

MeSH terms

  • Annexin A2* / genetics
  • Annexin A2* / metabolism
  • Arthritis, Rheumatoid* / genetics
  • Arthritis, Rheumatoid* / metabolism
  • Arthritis, Rheumatoid* / physiopathology
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Enzyme Activation / genetics
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Expression Profiling
  • Humans
  • MAP Kinase Signaling System*
  • Osteoarthritis / genetics
  • Osteoarthritis / metabolism
  • Osteoarthritis / physiopathology
  • Phosphorylation / genetics
  • Protein Binding / genetics
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Synoviocytes* / cytology
  • Synoviocytes* / metabolism

Substances

  • Annexin A2
  • ANXA2 protein, human
  • RNA, Long Noncoding