Abstract
BackgroundThe 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.MethodsWe 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.ResultsThe 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.ConclusionThis 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.
Highlights
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with complicated clinical manifestations and leads to multiple systemic impairments
peripheral blood mononuclear cells (PBMCs) exhibiting differential expression of long noncoding RNAs (lncRNAs) may be due to a change in the number of a cell type dendritic cells (DCs) from systemic lupus erythematosus (SLE) patients produce much higher levels of the IFN-α
In this study, we use full high-throughput sequencing to analyze the differences in the expression profiles of lncRNAs, miRNAs, and mRNAs in the PBMCs of patients with SLE at the genome-wide level
Summary
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with complicated clinical manifestations and leads to multiple systemic impairments. The main features of SLE are the presence of numerous pathogenic autoantibodies, complement depletion, and chronic inflammation. 150 cases of SLE occur among 100,000 people. Among people suffering from SLE for 5 years, those with kidney failure or died account for 15% [2]. The precise pathogenesis of SLE remains unclear. 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. 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
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