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Full high-throughput sequencing analysis of differences in expression profiles of long noncoding RNAs and their mechanisms of action in systemic lupus erythematosus.

ABSTRACT: BACKGROUND:The specific function of long noncoding RNAs (lncRNAs) in systemic lupus erythematosus (SLE) and the mechanism of their involvement in related pathological changes remain to be elucidated, so, in this study, we analyzed the differences in the expression profiles of lncRNAs and their mechanisms of action in SLE using full high-throughput sequencing, bioinformatics, etc. methods. METHODS:We used high-throughput sequencing to detect differences in the expression profiles of lncRNAs, miRNAs, and mRNAs in PBMCs from patients with SLE at the genome-wide level. Next, we predicted target genes of 30 lincRNAs (long intergenic noncoding RNAs) by constructing a coexpression network of differential lincRNAs and mRNAs and identified the role of lincRNAs. Then, we analyzed the coexpression network of 23 optimized lincRNAs and their corresponding 353 miRNAs, evaluated the cis- and trans-effects of these lincRNAs, and performed GO and KEGG analyses of target genes. We also selected 8 lincRNAs and 2 newly discovered lncRNAs for q-PCR validation and lncRNA-miRNA-mRNA analysis. Finally, we also analyzed respectively the relation between lncRNAs and gender bias in SLE patients using RT-qPCR, the relation between Systemic Lupus Erythematosus Disease Activity Index score and the "IFN signature" using ELISA, and the relation between the differential expression of lncRNAs and a change in the number of a cell type of PBMCs in SLE patients using RT-qPCR. RESULTS:The profiles of 1087 lncRNAs, 102 miRNAs, and 4101 mRNAs in PBMCs significantly differed between patients with SLE and healthy controls. The coexpression network analysis showed that the network contained 23 lincRNAs and 353 mRNAs. The evaluation of the cis- and trans-effects showed that the 23 lincRNAs acted on 704 target genes. GO and KEGG analyses of the target genes predicted the biological functions of the 23 lincRNAs. q-PCR validation showed 7 lincRNAs and 2 novel lncRNAs were identical to the sequencing results. The ceRNA network contained 7 validated lincRNAs, 15 miRNAs, and 155 mRNAs. In addition, the differential expression of lncRNAs may be gender dependent in SLE patients, SLE patients also exhibit a robust "IFN signature," and PBMCs exhibiting differential expression of lncRNAs may be due to a change in the number of a cell type. CONCLUSION:This work determined specific lncRNAs that play important biological functions in the pathogenesis of lupus and provided a new direction for diagnosis and treatment of disease.

SUBMITTER: Ye H

PROVIDER: S-EPMC6402184 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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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.

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Full high-throughput sequencing analysis of differences in expression profiles of long noncoding RNAs and their mechanisms of action in systemic lupus erythematosus.

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