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

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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.

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Authors and Affiliations

  1. Department of Training Sports Medicine, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, China

    Yongjian Liang

  2. Department of Orthopedic, The First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China

    Yongjian Liang

  3. Department of Orthopedic, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, China

    He Li

  4. Department of Anesthesiology, Affiliated Jining No. 1 , People’s Hospital of Jining Medical University, Jining Medical Universit, Jining, 272000, Shandong, China

    Chao Ding

  5. Department of Spinal Surgery, Jining No. 1 People’s Hospital, No. 6 Jiankang Road, Jining, 272000, Shandong, China

    Xianbin Gong

  6. Affiliated Jining No. 1 People’s Hospital of Jining Medical University, Jining Medical University, Jining, 272000, Shandong, China

    Xianbin Gong

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  1. Yongjian Liang
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Correspondence to Xianbin Gong.

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This study obtained approval from the Ethics Committee of our hospital and all participants signed the written informed consent.

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Liang, Y., Li, H., Gong, X. et al. Long Non-coding RNA THRIL Mediates Cell Growth and Inflammatory Response of Fibroblast-Like Synoviocytes by Activating PI3K/AKT Signals in Rheumatoid Arthritis. Inflammation 43, 1044–1053 (2020). https://doi.org/10.1007/s10753-020-01189-x

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  • DOI: https://doi.org/10.1007/s10753-020-01189-x

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