LncRNA linc00152/NF-κB feedback loop promotes fibroblast-like synovial cells inflammation in rheumatoid arthritis via regulating miR-103a/TAK1 axis and YY1 expression.

Introduction: Overexpressed inflammatory cytokines are the main factors causing rheumatoid arthritis (RA) tissue damage and pathological deterioration, and lncRNAs has found to beinvolved in some autoinflammatory diseases.

Methods: We designed this study to investigate the effect of lncRNA linc00152 on rheumatoid arthritis inflammation and explore its molecular mechanism. Result: We found that linc00152 was not only up-regulated in rheumatoid arthritis fibroblast-like synoviocytes (RAFLS), but also stimulated by TNF-α/IL-1β in adose- and time-dependent manner in RAFLS and this expression depends on the NF-κB signaling pathway. Conversely, linc00152 promoted TNF-α/IL-1β expression in RAFLS induced by TNF-α/IL-1β. In addition, we found that linc00152 promoted TAK1 expression by targeting inhibition of miR-103a and activated TAK1-mediated NF-κB pathway. NF-kB indirectly promotes linc00152 expression by promoting the transcription activity of YY1, and YY1 directly promotes linc00152 expression by binding the promoter of linc00152.

Conclusion: Our data suggested that the linc00152/NF-κB feedback loop promotes RAFLS inflammation via regulating miR-103a/TAK1 axis and YY1 expression. Thus, linc00152 acts as a switch to control this regulatory circuit and may serve as a diagnostic and therapeutic target for RA treatment.