Paeoniflorin Suppresses Rheumatoid Arthritis Development via Modulating the Circ-FAM120A/miR-671-5p/MDM4 Axis

Inflammation. 2021 Dec;44(6):2309-2322. doi: 10.1007/s10753-021-01504-0. Epub 2021 Aug 23.

Abstract

Paeoniflorin is an active ingredient derived from Paeonia, which has an anti-inflammatory effect. However, the potential role and basis of paeoniflorin in rheumatoid arthritis (RA) are indistinct. Cell viability, cycle distribution, migration, and invasion were evaluated via Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assays. The contents of inflammatory cytokines were examined using enzyme-linked immunosorbent assay (ELISA). RNA expression levels were determined via qRT-PCR and western blot. The targeting relationship between miR-671-5p and circ-FAM120A (hsa_circ_0003972) or murine double minute 4 (MDM4) was validated via dual-luciferase reporter assay. Paeoniflorin restrained proliferation, migration, invasion, and inflammation and accelerated cell cycle arrest in RA fibroblast-like synoviocytes (RA-FLSs). Circ-FAM120A was boosted in RA synovial tissues and RA-FLSs. Circ-FAM120A upregulation, miR-671-5p knockdown, or MDM4 augmentation reversed the repressive effect of paeoniflorin on RA-FLS progression. Moreover, paeoniflorin attenuated RA-FLS progression by regulating the circ-FAM120A/miR-671-5p/MDM4 axis. Paeoniflorin inhibited RA-FLS proliferation, mobility, and inflammation and triggered cell cycle arrest via mediating the circ-FAM120A/miR-671-5p/MDM4 pathway.

Keywords: Circ-FAM120A; Paeoniflorin; Rheumatoid arthritis; mDM4; miR-671-5p.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Antirheumatic Agents / pharmacology*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology
  • Case-Control Studies
  • Cell Cycle Checkpoints / drug effects
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cytokines / metabolism
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Glucosides / pharmacology*
  • Humans
  • Inflammation Mediators / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Monoterpenes / pharmacology*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Signal Transduction
  • Synoviocytes / drug effects*
  • Synoviocytes / metabolism
  • Synoviocytes / pathology

Substances

  • Anti-Inflammatory Agents
  • Antirheumatic Agents
  • Cell Cycle Proteins
  • Cytokines
  • Glucosides
  • Inflammation Mediators
  • MDM4 protein, human
  • MIRN671 microRNA, human
  • MicroRNAs
  • Monoterpenes
  • Proto-Oncogene Proteins
  • RNA, Circular
  • peoniflorin