Tetrandrine-induced downregulation of lncRNA NEAT1 inhibits rheumatoid arthritis progression through the STAT3/miR-17-5p pathway

Immunopharmacol Immunotoxicol. 2022 Dec;44(6):886-893. doi: 10.1080/08923973.2022.2092748. Epub 2022 Jul 11.

Abstract

Background: The inhibitory effect of Tetrandrine (Tet) on rheumatoid arthritis (RA) is well established. However, its exact molecular mechanism remains unknown.

Methods: RT-qPCR coupled with western blotting was employed to analyze the expression of NEAT1, miR-17-5p, and STAT3 in RA tissues and/or RA-fibroblast-like synoviocytes (RA-FLS) treated with 3 μmol/L of Tet for 48 h. Cell Counting Kit-8 assay and flow cytometry were performed to assess RA-FLS proliferation and apoptosis. Luciferase reporter assays were used to validate the interactions between miR-17-5p and STAT3 or NEAT1.

Results: The expression of NEAT1 decreased in a time-dependent manner upon Tet treatment. Tet significantly inhibited RA-FLS proliferation and triggered apoptosis by downregulating NEAT1 expression. Additionally, NEAT1 directly targeted miR-17-5p to upregulate STAT3 expression. Tet-induced low NEAT1 expression impaired RA-FLS growth by targeting miR-17-5p and inhibiting STAT3.

Conclusion: Tet exerts its inhibitory role in RA progression by regulating the NEAT1/miR-17-5p/STAT3 pathway.

Keywords: Rheumatoid arthritis; STAT3; lncRNA NEAT1; miR-17-5p.

MeSH terms

  • Arthritis, Rheumatoid* / drug therapy
  • Arthritis, Rheumatoid* / genetics
  • Humans
  • MicroRNAs* / genetics
  • RNA, Long Noncoding* / genetics
  • STAT3 Transcription Factor / genetics

Substances

  • RNA, Long Noncoding
  • MicroRNAs
  • STAT3 protein, human
  • STAT3 Transcription Factor
  • MIRN17 microRNA, human