New findings: What is the central question of this study? What are the functions of long non-coding (lnc) RNA OIP5-AS1 in development of rheumatoid arthritis inflammation and what is the molecular mechanism? What is the main finding and its importance? LncRNA OIP5-AS1 mitigates rheumatoid arthritis progression through the competitive endogenous RNA network involving the miR-448-paraoxonase 1 axis and through the inactivation of the toll-like receptor 3-nuclear factor κB signalling pathway. This study may offer new ideas for molecularly based control of rheumatoid arthritis.
Abstract: Rheumatoid arthritis (RA) is an autoimmune disorder with dysregulation of long non-coding RNAs (lncRNAs) possibly involved. This study aimed to inquire into the roles of lncRNA OIP5-AS1 in RA progression. A rat model of RA was induced. Overexpression of OIP5-AS1 was introduced in the model rats, and the changes in paw swelling, RA severity and the inflammatory factors interleukin (IL)-1β, IL-10, IL-6 and tumour necrosis factor α were measured. Fibroblast-like synoviocytes (FLSs) from RA patients were collected for in vitro experiments. A gain- and loss-of function study of OIP5-AS1, miR-448 and paraoxonase 1 (PON1) was performed to explore their roles in RA-FLS growth, apoptosis and inflammation. A toll-like receptor 3 (TLR3)-specific agonist, polyinosine-polycytidylic acid, or a nuclear factor κB (NF-κB)-specific antagonist, QNZ, was administrated in RA-FLSs. Consequently, overexpression of OIP5-AS1 reduced the symptom severity and the levels of inflammatory factors in RA rats. OIP5-AS1 could bind to miR-448 to up-regulate PON1 expression. Further overexpression of miR-448 reversed the effects of OIP5-AS1, while overexpression of PON1 inhibited RA-FLS growth and inflammation. In addition, TLR3 activation promoted RA progression. To conclude, this study evidenced that lncRNA OIP5-AS1 may mitigate RA progression through the miR-448-PON1 axis and through the inactivation of the TLR3-NF-κB signalling pathway.
Keywords: TLR3/NF-κB signalling pathway; long non-coding RNA OIP5-AS1; microRNA-448; paraoxonase 1; rheumatoid arthritis.
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