Abstract
BackgroundSystemic lupus erythematosus (SLE) is a chronic and incurable autoimmune disease involving the dysfunction of lymphocytes. Circular RNAs (circRNAs) are noncoding RNAs (ncRNAs) with a covalently closed loop structure, with abnormal expression in various human diseases may participate in the pathogenesis, while further study is needed in SLE. In this study, we aimed to find the circRNAs abnormally expressed in SLE and explore the function of circRNAs in SLE.MethodsCircRNA sequencing was used to find the abnormally expressed circRNA and qRT-PCR was used to detect the expression. Correlation analysis was used to analyze the correlation between circIBTK or miR-29b and clinicopathological variables in patients with SLE. Cell culture, nuclear-cytoplasmic fractionation, qRT-PCR, transfection, luciferase reporter assay, western blot analysis, DNA extraction and global methylation analysis were used to explain the function of circIBTK and miR-29b in the progression of SLE. SPSS 18.0 software was used to perform statistics.ResultsWe found that the expression of circIBTK was downregulated in SLE and correlated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, anti-double-stranded (ds)DNA and complement C3 level in patients with SLE. Then miR-29b expression was upregulated in SLE and correlated with SLEDAI score, anti-dsDNA and complement C3 level in patients with SLE. Mechanistic investigations indicated that miR-29b could induce DNA demethylation and activate the AKT signaling pathway and circIBTK might reverse the DNA demethylation and activation of the AKT signaling pathway induced by miR-29b via binding to miR-29b in SLE.ConclusionsCircIBTK was downregulated in SLE and might regulate DNA demethylation and the AKT signaling pathway via binding to miR-29b in SLE. CircIBTK and miR-29 could also act as biomarkers and therapeutic targets for SLE.
Highlights
Systemic lupus erythematosus (SLE) is a chronic and incurable autoimmune disease involving the dysfunction of lymphocytes
CircIBTK expression was downregulated in SLE and correlated with clinicopathological variables in patients with SLE To screen the Circular RNA (circRNA) expression profiles in SLE, we first performed circRNA sequencing to find the differently expressed circRNAs in the peripheral blood mononuclear cells (PBMCs) of patients with SLE compared to healthy controls (HC) (Table 1)
The results showed that DNA methylation levels were increased when PBMCs were transfected with circIBTK expression plasmids or miR-29b inhibitor and decreased when PBMCs were transfected with circIBTK small interfering RNA (siRNA) or miR-29b mimics (Fig. 4d and e)
Summary
Systemic lupus erythematosus (SLE) is a chronic and incurable autoimmune disease involving the dysfunction of lymphocytes. Circular RNAs (circRNAs) are noncoding RNAs (ncRNAs) with a covalently closed loop structure, with abnormal expression in various human diseases may participate in the pathogenesis, while further study is needed in SLE. Systemic lupus erythematosus (SLE) is a chronic and incurable autoimmune disease, which involves multiple organs, including skin, kidneys, and central nervous system [1, 2]. Circular RNAs (circRNAs) are noncoding RNAs (ncRNAs) with a covalently closed loop structure without 5′ cap and a 3′ polyadenylated tail. They are highly stable and widely exist in eukaryotic cells. More and more studies have demonstrated that circRNAs are expressed abnormally in many human diseases and might play a significant role in the pathogenesis and diagnosis of these diseases [9,10,11,12,13]
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