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Differential Plasma Expression Profiles of Long Non-Coding RNAs Reveal Potential Biomarkers for Systemic Lupus Erythematosus.

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.

SUBMITTER: Wu GC

PROVIDER: S-EPMC6627908 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Differential Plasma Expression Profiles of Long Non-Coding RNAs Reveal Potential Biomarkers for Systemic Lupus Erythematosus.

Wu Guo-Cui GC Hu Yan Y Guan Shi-Yang SY Ye Dong-Qing DQ Pan Hai-Feng HF

Biomolecules 20190528 6

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 ident ...[more]

PMID: 31141998

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Project description:ObjectiveTo evaluate the specificity of expression patterns of cell-free circulating microRNAs (miRNAs) in systemic lupus erythematosus (SLE).MethodsTotal RNA was purified from plasma, and 45 different specific, mature miRNAs were determined using quantitative reverse transcription-polymerase chain reaction assays. A total of 409 plasma samples were obtained from 364 different patients with SLE, healthy control subjects, and control subjects with other autoimmune diseases. The results in the primary cohort of 62 patients with SLE and 29 healthy control subjects were validated in 2 independent cohorts: a validation cohort comprising 68 patients with SLE and 68 healthy control subjects, and a disease control cohort comprising 20 patients with SLE (19 of whom were from the other validation cohort), 46 healthy control subjects, 38 patients with vasculitis, 18 patients with rheumatoid arthritis, and 20 immunosuppressed patients.ResultsSeven miRNAs were statistically significantly differentially expressed in plasma from patients with SLE. The expression of miRNA-142-3p (miR-142-3p) and miR-181a was increased, and the expression of miR-106a, miR-17, miR-20a, miR-203, and miR-92a was decreased. In addition, the expression of miR-342-3p, miR-223, and miR-20a was significantly decreased in SLE patients with active nephritis. A predictive model for SLE based on 2 or 4 miRNAs differentiated patients with SLE from control subjects (76% accuracy) when validated independently (P < 2 × 10(-9) ). Use of the 4-miRNA model provided highly significant differentiation between the SLE group and disease controls, except for those with vasculitis.ConclusionCirculating miRNAs are systematically altered in SLE. A 4-miRNA signature was diagnostic of SLE, and a specific subset of miRNA profiles was associated with nephritis. All of the signature miRNAs target genes in the transforming growth factor β signaling pathways. Other targets include regulation of apoptosis, cytokine-cytokine receptors, T cell development, and cytoskeletal organization. These findings highlight possible dysregulated pathways in SLE and suggest that circulating miRNA patterns distinguish SLE from other immunoinflammatory phenotypes.

Dataset Information

Differential Plasma Expression Profiles of Long Non-Coding RNAs Reveal Potential Biomarkers for Systemic Lupus Erythematosus.

Publications

Differential Plasma Expression Profiles of Long Non-Coding RNAs Reveal Potential Biomarkers for Systemic Lupus Erythematosus.

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