Circ_0088036 mediated progression and inflammation in fibroblast-like synoviocytes of rheumatoid arthritis by miR-1263/REL-activated NF-κB pathway

Xiaoyuan Wang; Dan Liu; Guofeng Cui; Haili Shen

doi:10.1016/j.trim.2022.101604

Circ_0088036 mediated progression and inflammation in fibroblast-like synoviocytes of rheumatoid arthritis by miR-1263/REL-activated NF-κB pathway

Transpl Immunol. 2022 Aug:73:101604. doi: 10.1016/j.trim.2022.101604. Epub 2022 Apr 20.

Authors

Xiaoyuan Wang¹, Dan Liu², Guofeng Cui³, Haili Shen⁴

Affiliations

¹ Department of Rheumatology and Immunology, Second Hospital of Lanzhou University, Lanzhou, Gansu, China.
² Departement of Rheumatology and Immunology, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, China.
³ Department of Orthopedics, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan, China.
⁴ Department of Rheumatology and Immunology, Second Hospital of Lanzhou University, Lanzhou,Gansu 730030,China. Electronic address: shenhaillzu@163.com.

PMID: 35460876
DOI: 10.1016/j.trim.2022.101604

Abstract

Background: Rheumatoid arthritis (RA) is a common joint disease with abnormal development of human fibroblast-like synoviocytes (HFLS). Circular RNAs (circRNAs) have essential regulation in the disease progression, and this study was to explore the regulatory mechanism of circ_0088036 in RA.

Methods: RNA expression analysis was performed through reverse transcription-quantitative polymerase chain reaction assay. Cell experiments were conducted by Cell Counting Kit-8 assay for cell viability, EdU (5-ethynyl-2'-deoxyuridine) assay for proliferation and flow cytometry for cell cycle or apoptosis. The protein detection was conducted using western blot. Enzyme-linked immunosorbent assay (ELISA) was used to examine the inflammatory cytokines. The binding identification was carried out through dual-luciferase reporter assay, RNA immunoprecipitation assay and pull-down assay.

Results: The level of circ_0088036 RNA was significantly upregulated in sera and in HFLS cells of RA patients. Targeted silencing of circ_0088036 restrained proliferation, cell cycle progression and inflammatory reaction through promoted the apoptosis of HFLS-RA cells via inhibiting the NF-κB pathway. The miR-1263 was identified as a target of circ_0088036. MiR-1263 was found to be down-regulated in sera and in HFLS cells of RA patients. The regulatory effects of circ_0088036 on HFLS-RA cells were attributed to inhibit the miR-1263 level. REL is a susceptibility locus for certain autoimmune diseases. MiR-1263 directly targeted REL, which was discovered to be elevated in sera and HFLS cells of RA patients, and circ_0088036 interacted with miR-1263 to affect REL expression. Functionally, overexpression of miR-1263 suppressed the development of HFLS-RA by blocking the NF-κB pathway, and this phenomenon was reversed by the upregulation of REL.

Conclusion: These findings suggested that circ_0088036/miR-1263/REL/NF-κB pathway was involved in the functional development of HFLS-RA cells, indicating a novel molecular network in RA progression in vitro.

Keywords: Fibroblast-like synoviocytes; REL; Rheumatoid arthritis; circ_0088036; miR-1263.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis
Arthritis, Rheumatoid* / genetics
Arthritis, Rheumatoid* / metabolism
Cell Proliferation / genetics
Cells, Cultured
Fibroblasts
Humans
Inflammation / metabolism
MicroRNAs* / genetics
NF-kappa B / genetics
NF-kappa B / metabolism
Synoviocytes* / metabolism

Substances

MicroRNAs
NF-kappa B