LncRNA XIST promotes adjuvant-induced arthritis by increasing the expression of YY1 via miR-34a-5p

Abstract

Objectives: This study aims to explore the mechanism by which long non-coding ribonucleic acids (lncRNA) X-inactive specific transcript (XIST) affects the progression of adjuvant-induced arthritis (AIA).

Materials and methods: Freund's complete adjuvant was used to induce arthritis in rats. The polyarthritis, spleen and thymus indexes were calculated to evaluate AIA. Hematoxylin-eosin (H&E) staining was used to reveal the pathological changes in the synovium of AIA rats. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the expression of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 and IL-8 in the synovial fluid of AIA rats. The cell continuing kit (CCK)-8, flow cytometry, and Transwell assays were used to assess the proliferation, apoptosis, migration and invasion of transfected fibroblast-like synoviocytes (FLS) isolated from AIA rats (AIA-FLS). Dual-luciferase reporter assay was performed to verify the binding sites between XIST and miR-34b-5p or between YY1 mRNA and miR-34b-5p.

Results: The XIST and YY1 were highly expressed, and miR-34a-5p was lowly expressed in the synovium of AIA rats and in AIA-FLS. Silencing of XIST impaired the function of AIA-FLS in vitro and inhibited the progression of AIA in vivo. The XIST promoted the expression of YY1 by competitively binding to miR-34a-5p. Inhibition of miR-34a-5p strengthened the function of AIA-FLS by upregulating XIST and YY1.

Conclusion: The XIST controls the function of AIA-FLS and may promote the progression of rheumatoid arthritis via the miR-34a-5p/YY1 axis.

Citation: Wei Y, Dai Y, Deng Y, Ye Z. LncRNA XIST promotes adjuvant-induced arthritis by increasing the expression of YY1 via miR-34a-5p. Arch Rheumatol 2023;38(1):82-94.

All animal experiments were carried out under the approval from the Ethics Committee of Shenzhen Futian Hospital for Rheumatic Diseases and followed the regulations for experiment animal use set by the committee as well as the Guidelines for the Care and Use of Laboratory Animals issued by the National Institutes of Health (ethical approval number: FS202002002). The study was conducted in accordance with the principles of the Declaration of Helsinki.

Data Sharing Statement:
The data that support the findings of this study are available from the corresponding author upon reasonable request.

Conceived the ideas, provided critical materials, supervised the study: W.Y.Z., Y.Z.Z.; Designed the experiments, analyzed the data: W.Y.Z., Y.Z.Z., D.L.P.; Performed the experiments: W.Y.Z., Y.Z.Z., D.L.P. D.Y.Q.; Wrote the manuscript: W.Y.Z., D.L.P., D.Y.Q.; All the authors have read and approved the final version for publication.

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

This research was funded by commonweal research project in public health of Futian District, Shenzhen in 2020 (project no.: FTWS2020052).