Abstract
Identify long non-coding RNAs (lncRNAs) that might serve as biomarkers for systemic lupus erythematosus (SLE) and explore the biological functions of the identified lncRNAs. In the screening phase, we examined the lncRNA expression profile of plasma samples from 24 patients with SLE and 12 healthy controls (HCs) using lncRNA microarray with pooled samples. The candidate lncRNAs were verified in individual samples by quantitative real-time (qRT)-PCR. In the independent validation stage, the identified lncRNAs were evaluated in 240 patients with SLE and 120 HCs. The identified lncRNAs were assessed further in an external validation stage including patients with rheumatoid arthritis (RA) and primary Sjögren’s syndrome (pSS). In addition, we constructed correlated expression networks including coding–non-coding co-expression and competing endogenous RNAs (ceRNAs). Plasma levels of linc0597, lnc0640, and lnc5150 were elevated in SLE patients compared with those of HCs, whereas levels of GAS5 and lnc7074 were decreased. Five lncRNAs were identified as potential SLE biomarkers with an area under the receiver operating characteristic curve (AUC) ranging from 0.604 to 0.833 in the independent validation phase. This panel of five lncRNAs had high diagnostic accuracy for SLE (AUC = 0.966) and distinguished SLE from RA and pSS (AUC = 0.683 and 0.910, respectively). Co-expression analysis showed that GAS5, lnc0640, and lnc5150 may participate in the SLE pathogenesis through the MAPK pathway. The ceRNA network indicated that GAS5, lnc0640, lnc3643, lnc6655, and lnc7074 bind competitively with microRNAs regulating the expression of target genes. Aberrant expression and related pathways suggest the important role of lncRNAs in SLE pathogenesis. In addition, the panel of five lncRNAs (GAS5, lnc7074, linc0597, lnc0640, and lnc5150) in plasma could be used as SLE biomarkers.
Highlights
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease of variable severity; its etiology is multifactorial, mainly involving genetic, epigenetic, and environmental factors [1]
The competing endogenous RNAs (ceRNAs) analysis pointed out that growth arrest-specific 5 (GAS5), lnc0640, lnc3643, lnc6655, and lnc7074 could act as ceRNAs to regulate the expression of the predicted target genes by competing for common miRNA-binding sites with mRNAs (Figure S8)
Molad et al reported that the activity of two members of the MAPK family, namely, ERK and JNK, are associated with systemic lupus erythematosus (SLE) disease activity [40]. long non-coding RNAs (lncRNAs)–mRNA co-expression network analysis showed that GAS5, lnc0640, and lnc5150 may participate in the development of SLE
Summary
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease of variable severity; its etiology is multifactorial, mainly involving genetic, epigenetic, and environmental factors [1]. It is a heterogeneous disease and no single clinical characteristic or laboratory test is diagnostic. The exact pathogenesis of SLE remains unclear, it is known that its etiology is multifactorial mainly involving genetic, epigenetic, and environmental factors [1,3]. Increasing evidence suggests that lncRNAs play a critical role in the pathogenesis of autoimmune diseases, such as SLE, rheumatoid arthritis (RA), Sjögren’s syndrome (SS), etc. Increasing evidence suggests that lncRNAs play a critical role in the pathogenesis of autoimmune diseases, such as SLE, rheumatoid arthritis (RA), Sjögren’s syndrome (SS), etc. [11,12,13,14,15]
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