Down-Regulation of LOC645166 in T Cells of Ankylosing Spondylitis Patients Promotes the NF-κB Signaling via Decreasingly Blocking Recruitment of the IKK Complex to K63-Linked Polyubiquitin Chains.
Ankylosing spondylitis (AS) is a chronic inflammatory disease that mainly affects the spine. AS is highly associated with the expression of HLA-B27. Up to 95% AS patients are HLA-B27-positive. However, only 1%-2% of the HLA-B27-positive carriers suffer from AS, implying that other factors may also govern the development of AS. Long non-coding RNAs (lncRNAs) can regulate the immune response via their binding proteins. In the present study, we have identified that the levels of lncRNA, LOC645166, in T cells of AS patients were reduced. Overexpression of LOC645166 in Jurkat cells down-regulated the IL-23p19 expression and suppressed the JAK2/STAT3 signaling in response to stimulation by phorbol 12-myristate 13-acetate. Suppression of STAT3 activation by LOC645166 was also observed when Jurkat cells or T cells of AS patient were treated with anti-CD3/CD28 antibodies. In order to explore the role of LOC645166 in the pathogenesis of AS, RNA pull-down assay plus proteomic approach and western blotting were performed and identified that LOC645166 prefers binding the K63-linked polyubiquitin chains. LOC645166 can suppress recruitment of the IKK complex to K63-linked polyubiquitin chains and diminish IKK2 activation, leading to down-regulation of NF-κB activation. Down-regulation of LOC645166 expression in T cells of AS patients up-regulates NF-kB activation via decreasingly impeding recruitment of the IKK complex to K63-linked polyubiquitin chains, allowing AS patients to exhibit more sensitivity to stimulation by the proinflammatory cytokines or by TLR ligands.
['Yu|Hui-Chun|HC|', 'Huang|Kuang-Yung|KY|', 'Lu|Ming-Chi|MC|', 'Huang Tseng|Hsien-Yu|HY|', 'Liu|Su-Qin|SQ|', 'Lai|Ning-Sheng|NS|', 'Huang|Hsien-Bin|HB|']
D015415:Biomarkers D016207:Cytokines D004198:Disease Susceptibility D005786:Gene Expression Regulation D006801:Humans D051550:I-kappa B Kinase D018836:Inflammation Mediators D016328:NF-kappa B D021381:Protein Transport D062085:RNA, Long Noncoding D015398:Signal Transduction D013167:Spondylitis, Ankylosing D013601:T-Lymphocytes D054875:Ubiquitination
LOC645166 ankylosing spondylitis polyubiquitin NF- kappa B long noncoding RNA