Hsa_circ_0000479 as a Novel Diagnostic Biomarker of Systemic Lupus Erythematosus.

Background: Accumulating evidence suggests that differentially expressed non-coding circular RNAs (circRNAs) play critical roles in the progress of autoimmune diseases. However, the role of circRNAs in systemic lupus erythematosus (SLE) remains unclear. Methods: We initially used next-generation sequencing (NGS) to comprehensively analyze circRNA expression profiles in peripheral blood mononuclear cells (PBMCs) from 10 SLE patients, stratified by their disease activity characteristics (stable or active SLE), and 10 healthy controls (HCs). Candidate circRNAs identified were first validated by quantitative reverse-transcription (qRT)-PCR in PBMC samples from a training-phase cohort of five SLE patients and five HCs. The significantly dysregulated circRNAs were then confirmed by qRT-PCR in a validation cohort of 23 SLE patients and 21 HCs, and in an external validation cohort with 64 SLE patients, 58 HCs, and 50 patients with rheumatoid arthritis (RA). In addition, we conducted bioinformatics analysis and western blotting investigating the relationships between the candidate circRNAs and SLE progression. Results: Multilayer integrative analysis of circRNA regulation showed that 84 circRNAs were upregulated and 30 were downregulated in patients with SLE compared with HCs. We then analyzed the intersection of these differentially expressed circRNAs in an SLE-stable cohort, an SLE-active cohort, and HCs. This enabled us to narrow down dysregulated circRNAs to 15 upregulated circRNAs. Only hsa_circ_0000479 was significantly upregulated in PBMCs of patients with SLE compared with HCs (P < 0.05). Furthermore, the diagnostic potential of hsa_circ_0000479 expression to distinguish SLE patients from HCs and RA patients was also significantly increased in the validation-phase and external-validation-phase cohorts (P < 0.05). When distinguishing SLE patients from HCs, the diagnostic specificities of hsa_circ_0000479 were 0.619 and 1.0 in two validation cohorts, respectively (AUCs = 0.731 and 0.730, respectively). It was also significantly increased in either stable SLE patients or active SLE patients compared with HCs in these two cohorts (P < 0.05). We also used bioinformatics analysis to show that hsa_circ_0000479 regulates SLE progression by modulating metabolic pathways and the Wnt signaling pathway. Western blotting revealed that the expression of Wnt-16 protein was significantly decreased in SLE. Conclusion: Our results suggest that hsa_circ_0000479 has potential as a novel biomarker for the diagnosis of SLE.

Guo G ，Wang H ，Ye L ，Shi X ，Yan K ，Lin K ，Huang Q ，Li B ，Lin Q ，Zhu L ，Xue X ，Zhang H ... -  《Frontiers in Immunology》

Expression profile and diagnostic value of circRNAs in peripheral blood from patients with systemic lupus erythematosus.

Luo Q ，Li X ，Fu B ，Zhang L ，Fang L ，Qing C ，Guo Y ，Huang Z ，Li J ... -  《-》

Identification of circular RNAs hsa_circ_0044235 and hsa_circ_0068367 as novel biomarkers for systemic lupus erythematosus.

Luo Q ，Zhang L ，Li X ，Fu B ，Guo Y ，Huang Z ，Li J ... -  《-》

Circular RNAs hsa_circ_0000479 in peripheral blood mononuclear cells as novel biomarkers for systemic lupus erythematosus.

Luo Q ，Zhang L ，Fang L ，Fu B ，Guo Y ，Huang Z ，Li J ... -  《-》

Circular RNA expression profile of systemic lupus erythematosus and its clinical significance as a potential novel biomarker.

Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that are more abundant, specific, and highly organized than linear RNAs. Increasing evidence supports that circRNAs may serve as diagnostic biomarkers in many diseases, but their potential as biomarkers in systemic lupus erythematosus (SLE) remains unclear. We investigated the critical circRNAs involved in SLE progression and explored their potential application as biomarkers in SLE. RNA sequencing was conducted on peripheral blood mononuclear cells (PBMCs) from 4 SLE patients and 4 healthy volunteers. CircRNA profile data were analyzed to identify differentially expressed circRNAs and visualized via R software. After screening, qPCR analysis of target circRNA expression was performed using PBMCs from 31 SLE patients and 35 healthy volunteers. Correlations between circRNA expression levels and the SLEDAI score were assessed via Spearman correlation analysis. Finally, the performance of circRNAs as biomarkers in SLE was examined by receiver operating characteristic curve analysis. The result identified six differentially expressed circRNAs between SLE patients and healthy controls: hsa_circ_0006689, hsa_circ_0070562, hsa_circ_0006117, hsa_circ_0007683, hsa_circ_0042519, and hsa_circ_0008647. The validation analysis showed differing relative expression levels of hsa_circ_0007683, hsa_circ_0042519, hsa_circ_0008647, and hsa_circ_0006689 between SLE patients and healthy volunteers (P < 0.05), and hsa_circ_0006689 expression in PBMCs correlated with the SLEDAI score (P < 0.05). Furthermore, addition of hsa_circ_0006689 expression increased the sensitivities of anti-dsDNA antibody and anti-Sm antibody levels for SLE diagnosis (from 29.03 to 61.30% and 32.26-71.00%, respectively). Our results suggest hsa_circ_0006689 may be a useful circRNA biomarker for SLE diagnosis and prognosis.

Li W ，Fan R ，Zhou C ，Wei Y ，Lin S ，Wen S ，Zeng W ，Hou W ，Zhao C ，Lin Y ... -  《-》