The Role And Mechanism Of The Regulation Of Hsa?circ?0012919-miR-125a In The Pathogenesis Of Systemic Lupus Erythematous

ObjectiveSystemic lupus erythematous(SLE)is an autoimmune disease characterized by production of autoantibodies directed against various autoantigens.But the expression profiles and functions of circRNAs in SLE are still scarce.MethodsSLE patients and healthy control subjects were recruited.CD4+T cells were isolated,circRNA microarray analysis were used to screen for circRNA candidate in CD4+T cells.Expression of DNMT1,CD11a and CD70 and methylation level of CD11a and CD70 were detected after transfecting hsa?circ?0012919-targeted siRNA.The network analysis of hsa?circ?0012919 was used by bioinformatics.Luciferase reporter assay and FISH assay were used for screen for which miRNAs could bind with hsa?circ?0012919.Finally,MRL/lpr mice model was used to verify the intervention effect of miRNA,including the proteinuria,antibodies and renal tissues.Results12 circRNAs were upregulated and 2 circRNAs were downregulated in SLE patients group after circRNA microarray analysis.Hsa?circ?0012919 was further confirmed to be significantly different between healthy control and SLE patients(p<0.05)and associated with SLE characters(p<0.05).Downregulation of hsa?circ?0012919 1)increased the expression of DNMT1 and reduced the expression of CD70,CD11a,2)reversed the DNA hypomethylation of CD11a and CD70 in CD4+T cells of systemic lupus erythematous,but it could be reversed by downregulation of DNMT1.Hsa?circ?0012919 regulated KLF13 and RANTES by miRNA-125a-3p.MiR-125a can improve lupus symptoms in MRL/lpr mice model.ConclusionsHsa?circ?0012919,miR-125a and their interaction play an important role in the pathogenesis of SLE.