Autoimmune rheumatologic diseases

Oral

atf3 Upregulates the Long Non-coding Rna Ntt in Peripheral Blood Mononuclear Cells of Rheumatoid Arthritis Patients

Wednesday, June 14
6:15 PM - 7:45 PM

Long non-coding RNAs (lncRNAs) exert essential functions via multiple mechanisms. There is emerging evidence that dysregulation of lncRNAs in immune cells might contribute to the pathogenesis of autoimmune diseases. The regulation and function of lncRNAs in rheumatoid arthritis (RA), a systemic autoimmune disease, remained largely unknown. Non-coding transcript in T cells (NTT) is a nuclear lncRNA first discovered in activated T cells. In this study, we also found NTT expression in monocytes and macrophages, and NTT was highly upregulated in peripheral blood mononuclear cells (PBMCs) of untreated RA patients. Further DNA Chromatin Immunoprecipitation (ChIP) assay revealed the binding of the transcription factor ATF3 on NTT promoter. Knockdown of ATF3 in THP-1 cell line decreased NTT expression. Moreover, knockdown of NTT in THP-1 showed markedly decreased expression of Prostate and Breast Cancer Overexpressed 1 (PBOV1), a gene in proximity with the chromosomal location of NTT. Both ATF3 and PBOV1 were found to be upregulated in PBMCs of untreated RA as compared with healthy controls. The level of PBOV1 in untreated RA even reached 5000~50000 fold higher than controls. Our study suggests that ATF3 mediates NTT and subsequent PBOV1 activation in RA PBMCs. NTT and PBOV1 expression levels could be sensitive diagnostic markers for new-onset RA.

Chin-An Yang

Department of Laboratory Medicine, China Medical University Hospital, Taiwan

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    Ju-Chen Yen

    Epigenomics Research Center, China Medical University Hospital

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      Yu-Chia Chen

      Epigenomics Research Center, China Medical University Hospital

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        Joung-Liang Lan

        Department of Rheumatology, China Medical University Hospital

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          Jan-Gowth Chang

          Department of Laboratory Medicine, China Medical University Hospital

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            atf3 Upregulates the Long Non-coding Rna Ntt in Peripheral Blood Mononuclear Cells of Rheumatoid Arthritis Patients



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