LncRNA THRIL is involved in the proliferation, migration, and invasion of rheumatoid fibroblast-like synoviocytes
ANNALS OF TRANSLATIONAL MEDICINE(2021)
摘要
Background: Fibroblast-like synoviocytes (FLSs), which can migrate and directly invade the cartilage and the bone, are crucial players in joint damage in rheumatoid arthritis (RA). Nevertheless, the detailed mechanisms underlying the aberrant activation of RA FLSs remain unclear. Several studies have attempted to explore the relationship between long non-coding RNAs (lncRNAs) and RA pathology; however, the role of lncRNAs in RA is unknown. The present study aimed to determine the functions of tumor necrosis factor-alpha and heterogeneous nuclear ribonucleoprotein L-related immunoregulatory lincRNA (THRIL) in RA FLSs migration and invasion. Methods: Small interfering RNA targeting THRIL or lentivirus overexpressing THRIL was used to knockdown or overexpress THRIL. Quantitative reverse transcription polymerase chain reaction (PCR) was employed for the detection of RNA expression. The proliferation rate of RA FLSs was measured using a 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay. Migration and invasion were detected using a transwell chamber. Downstream targets were identified using a human cell cycle real-time PCR array and a human cell motility real-time PCR array. Results: A significant decrease in THRIL expression was found in RA FLSs compared with cells from healthy control (HC)patients. THRIL is mainly localized in the nucleus. Knockdown of THRIL increased the proliferation, migration, and invasion of RA FLSs. In contrast, THRIL overexpression had the opposite effect. THRIL knockdown increased interleukin-10 (IL-10)-triggered expression of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13. THRIL overexpression led to a significant decrease in MMP-13 expression in response to stimulation with IL-10. Furthermore, we observed that the expression levels of cyclindependent kinase 1 (CDK1) and G2 and S phase-expressed-1 (GTSE1), both of which are associated with cellular mobility and proliferation, were downregulated with THRIL overexpression. Conclusions: Reduced expression of lncRNA THRIL represses the proliferation, migration, and invasion of RA FLSs, suggesting that lncRNA THRIL might be a potential target for RA therapy.
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关键词
Rheumatoid arthritis (RA),long non-coding RNA (lncRNA),migration,invasion
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