Abstract
BackgroundCertain circRNAs could be used as biomarkers to determine the risk of development and/or severity of systemic lupus erythematosus, and their new function in the regulation of gene expression has motivated us to investigate their role in SLEMethodsExperimental methods including qRT-PCR, RNA immunoprecipitation (RIP), pulldown, dual luciferase reporter assay, RNA interference and cell transfection, RNA fluorescence in situ hybridization, western blotting, and mass spectrometry were used to assessed circGARS (hsa_circRNA_0009000) for immune functions and defined mechanisms by which circGARS promotes the progression in SLE.ResultsOur results demonstrated that the levels of circGARS was remarkably upregulated in SLE and correlated with clinicopathological features. CircGARS directly combined with microRNA-19a (miR-19a). Functionally, circGARS downregulated the expression of TNFAIP3 (A20, tumor necrosis factor alpha-induced protein 3) to mediate the activation of immune responses that were regulated by the nuclear factor-κB (NF-κB) pathway as a negative feedback mechanism. In addition, miR-19a regulated A20 (TNFAIP3) degradation by downregulating the expression of YTH N6-methyladenosine RNA-binding protein 2 (YTHDF2).ConclusionsThe circGARS sponges miR-19a to regulate YTHDF2 expression to promote SLE progression through the A20/NF-κB axis and may act as an independent biomarker to help the treatment of SLE patients.
Highlights
Certain circRNAs could be used as biomarkers to determine the risk of development and/or severity of systemic lupus erythematosus, and their new function in the regulation of gene expression has motivated us to investigate their role in Systemic lupus erythematosus (SLE)
To investigate whether the abnormal activation of the A20/nuclear factor-κB (NF-κB) signaling pathway was regulated by circGARS, we studied how circGARS enhanced transcriptional levels by directly binding to m6A modification proteins, which might participate in the pathogenesis of SLE
The results showed that circGARS had a higher level of expression in SLE patients
Summary
Certain circRNAs could be used as biomarkers to determine the risk of development and/or severity of systemic lupus erythematosus, and their new function in the regulation of gene expression has motivated us to investigate their role in SLE. Systemic lupus erythematosus (SLE) is a chronic and systemic autoimmune disease with diverse clinical manifestations and complicated disease progression. The pathogenesis of SLE are still largely unknown. Mortality for patients with SLE has greatly declined, accurate diagnosis and better management of complications, especially the development of. There is an urgent need to gain an in-depth understanding the pathogenesis of SLE. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are two main kinds of noncoding RNAs that regulate the initiation and development of SLE [3, 4].
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