Long Non-coding RNA THRIL Mediates Cell Growth and Inflammatory Response of Fibroblast-Like Synoviocytes by Activating PI3K/AKT Signals in Rheumatoid Arthritis.

Abstract

The present study explored the possible functions and the underlying mechanism of tumor necrosis factor-α (TNF-α) and heterogeneous nuclear ribonucleoprotein L (hnRNPL)-related immunoregulatory lncRNA plasmacytoma variant translocation 1 (THRIL) in rheumatoid arthritis (RA). Serum samples were collected from patients with RA. Primary fibroblast-like synoviocytes (FLSs) were separated from synovial tissues and cultured for subsequent cell experiments by transfecting different vectors. The qRT-PCR analysis was employed for evaluating the levels of THRIL in the serum. Enzyme-linked immunosorbent assay (ELISA) analysis was employed to detect the levels of inflammatory cytokines. MTT assay and Annexin V-FITC/PI apoptosis assay were used to evaluate the cell viability and apoptosis, respectively. Besides, the levels of the apoptotic proteins and the pathway-related proteins were measured by western blotting. Pearson's correlation analysis was used to assess the correlation between THRIL and clinical parameters. THRIL was overexpressed in the blood of patients with RA as compared with healthy participants (p < 0.05). The THRIL levels in the RA blood sample were positively associated with TNF-α levels, DAS 28, and ESR (p < 0.001). TNF-α treatment significantly inhibited cell viability and enhanced cell apoptosis. Furthermore, it elevated the levels of IL-1β and MMP-3 (p < 0.05), whereas the suppression of THRIL reversed these effects in TNF-α-treated RA-FLSs (p < 0.05). Moreover, the reduced THRIL remarkably reduced the expression of p-PI3K and p-AKT (p < 0.05) in TNF-α-treated RA-FLSs. The present study revealed that THRIL could regulate cell growth and inflammatory response of FLSs by activating the PI3K/AKT signaling pathway, subsequently playing important roles in promoting the occurrence and development of RA.

• Authors: Yongjian Liang, He Li, Xianbin Gong, Chao Ding
• Journal: Inflammation (Inflammation) Vol. 43 Issue 3 Pg. 1044-1053 (Jun 2020) ISSN: 1573-2576 [Electronic] United States
• PMID: 32232711 (Publication Type: Journal Article)

Chemical References

• Membrane Transport Proteins
• RNA, Long Noncoding
• SEC62 protein, human
• Proto-Oncogene Proteins c-akt

Topics

• Adult
• Aged
• Arthritis, Rheumatoid (immunology, metabolism)
• Cell Proliferation (physiology)
• Cells, Cultured
• Female
• Fibroblasts (immunology, metabolism)
• Humans
• Male
• Membrane Transport Proteins (immunology, metabolism)
• Middle Aged
• Phosphatidylinositol 3-Kinases (immunology, metabolism)
• Proto-Oncogene Proteins c-akt (immunology, metabolism)
• RNA, Long Noncoding (immunology, metabolism)
• Synoviocytes (immunology, metabolism)