Research Paper Volume 13, Issue 21 pp 24071—24085

LncRNA MIR31HG is induced by tocilizumab and ameliorates rheumatoid arthritis fibroblast-like synoviocyte-mediated inflammation via miR-214-PTEN-AKT signaling pathway

Liang Cao1,2, *, , Haifeng Jiang3, *, , Jing Yang1, *, , Jun Mao2, , Guofeng Wei4, , Xiangyun Meng2, , Hongmei Zang1, ,

  • 1 School of Pharmacy, Anhui Medical University, Hefei, Anhui, China
  • 2 Department of Pharmacy, The Second People’s Hospital of Hefei, Hefei, Anhui, China
  • 3 Institute of Clinical Pharmacology, Anhui Medical University, Hefei, Anhui, China
  • 4 Department of Emergency, The Second People’s Hospital of Hefei, Hefei, Anhui, China
* Equal contribution

Received: May 18, 2021       Accepted: September 7, 2021       Published: November 9, 2021
How to Cite

Copyright: © 2021 Cao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Fibroblast-like synoviocytes (FLS) obtained from the joint synovium of rheumatoid arthritis (RA) patients exhibit hyperplasia and aggressive inflammatory phenotypes. This study was designed to explore the anti-inflammatory mechanism of IL-6R inhibitor, tocilizumab, in FLS-mediated inflammation in RA from the perspective of non-coding RNAs (ncRNAs). To this end, we sorted primary FLS obtained from the synovium of patients with RA and cultured them in vitro. The cells were then treated with tocilizumab and subjected to lncRNA- and miRNA-seq to identify the ncRNAs regulated by tocilizumab treatment using bioinformatic analysis and experimental verification. Tocilizumab treatment enhanced the expression of lncRNA MIR31HG and reduced that of micoRNA-214 (miR-214). In addition, miR-214 activated the AKT signaling pathway by directly targeting MIR31HG and PTEN. In addition, the tocilizumab-MIR31HG-miR-214-PTEN-AKT axis regulated the proliferation, migration, and production of inflammatory molecules and matrix metalloproteinases (MMPs) in RA-FLS. Furthermore, co-culture experiments showed that this axis could inhibit the inflammatory phenotype of macrophages and protect chondrocytes. In summary, our study shows that tocilizumab suppresses RA-FLS inflammation by regulating the MIR31HG-miR-214-PTEN-AKT pathway, and presents new insights on RA pathogenesis and potential targets for RA therapy.


RA: rheumatoid arthritis; FLS: fibroblast-like synoviocytes; ncRNA: non-coding RNAs; miR-214: micoRNA-214; MMPs: matrix metalloproteinases; ECM: extracellular matrix; ceRNA: Competing endogenous RNAs; NSCLC: non-small cell lung cancer; PAGE: polyacrylamide gel electrophoresis; qPCR: quantitative PCR; 3’UTR: 3’-untranslated region.