The circRNA-miRNA-mRNA regulatory network in plasma and peripheral blood mononuclear cells and the potential associations with the pathogenesis of systemic lupus erythematosus

Objectives This study aimed to explore the possible role of plasma and peripheral blood mononuclear cells (PBMCs) circular RNA (circRNA) in systemic lupus erythematosus (SLE).Method Total RNA was extracted from blood plasma samples obtained from 10 patients with SLE and 10 healthy controls and subjected to microarray analysis to define the profile of circRNA expression. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) amplification was conducted. The overlapped circRNA between PBMCs and plasma was performed, the interactions with microRNAs were predicted, the miRNA target mRNA was predicted, and the GEO database was used. The Gene ontology and pathway analysis was performed.Results One hundred thirty-one upregulated and 314 significantly downregulated circRNAs were identified in the plasma of patients with SLE by the Fold change criteria (>= 2.0) and P < 0.05. The qRT-PCR results showed that the expression of has-circRNA-102531, has-circRNA-103984, and has-circRNA-104262 was increased in plasma of SLE, and the expression of has-circRNA-102972, has-circRNA-102006, has-circRNA-104313 was decreased in plasma of SLE. Twenty-eight upregulated circRNAs and 119 downregulated circRNAs were overlapped from PBMCs and plasma, and ubiquitination was enriched. Furthermore, the circRNA-miRNA-mRNA network was constructed in SLE after analyzing dataset GSE61635 from GEO. The circRNA-miRNA-mRNA network comprises 54 circRNAs, 41 miRNAs, and 580 mRNAs. In addition, the TNF signaling pathway and the MAPK pathway were enriched from the mRNA of the miRNA target.Conclusion We first revealed the differentially expressed circRNAs in plasma and PBMCs, and then the circRNA-miRNA-mRNA network was constructed. The network's circRNAs could be a potential diagnostic biomarker and potentially play an important role in the pathogenesis and development of SLE.

Automated summary

This study investigated the role of circRNA in systemic lupus erythematosus (SLE) by analyzing its expression in plasma and peripheral blood mononuclear cells (PBMCs). Differentially expressed circRNAs were identified and their potential diagnostic and pathogenic roles in SLE were explored through network analysis.