Dataset Information

Integrative analysis of long non-coding RNAs and messenger RNA expression profiles in systemic lupus erythematosus.

ABSTRACT: Thousands of long noncoding RNAs (lncRNAs) have been reported and represent an important subset of pervasive genes associated with a broad range of biological functions. Abnormal expression levels of lncRNAs have been demonstrated in multiple types of human disease. However, the role of lncRNAs in systemic lupus erythematosus (SLE) remains poorly understood. In the present study, the expression patterns of lncRNAs and messenger RNAs (mRNAs) were investigated in peripheral blood mononuclear cells (PBMCs) in SLE using Human lncRNA Array v3.0 (8x60 K; Arraystar, Inc., Rockville, MD, USA). The microarray results indicated that 8,868 lncRNAs (3,657 upregulated and 5,211 downregulated) and 6,876 mRNAs (2,862 upregulated and 4,014 downregulated) were highly differentially expressed in SLE samples compared with the healthy group. Gene ontology (GO) analysis of lncRNA target prediction indicated the presence of 474 matched lncRNA?mRNA pairs for 293 differentially expressed lncRNAs (fold change, ?3.0) and 381 differentially expressed mRNAs (fold change, ?3.0). The most enriched pathways were 'Transcriptional misregulation in cancer' and 'Valine, leucine and isoleucine degradation'. Furthermore, reverse transcription?quantitative polymerase chain reaction data verified six abnormal lncRNAs and mRNAs in SLE. The results indicate that the lncRNA expression profile in SLE was significantly changed. In addition, a range of SLE?associated lncRNAs were identified. Thus, the present results provide important insights regarding lncRNAs in the pathogenesis of SLE.

SUBMITTER: Luo Q

PROVIDER: S-EPMC5802165 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Integrative analysis of long non-coding RNAs and messenger RNA expression profiles in systemic lupus erythematosus.

Luo Qing Q Li Xue X Xu Chuxin C Zeng Lulu L Ye Jianqing J Guo Yang Y Huang Zikun Z Li Junming J

Molecular medicine reports 20171222 3

Thousands of long noncoding RNAs (lncRNAs) have been reported and represent an important subset of pervasive genes associated with a broad range of biological functions. Abnormal expression levels of lncRNAs have been demonstrated in multiple types of human disease. However, the role of lncRNAs in systemic lupus erythematosus (SLE) remains poorly understood. In the present study, the expression patterns of lncRNAs and messenger RNAs (mRNAs) were investigated in peripheral blood mononuclear cells ...[more]

PMID: 29286106

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Project description:Long non-coding RNA (lncRNA) TUG1 acts as a proto-oncogene, allowing the proliferation of tumor cells, and it has been related to inflammation. Therefore, we aimed in this study to investigate for the first time the role of TUG1 gene polymorphism and the TUG1 level as biomarkers in systemic lupus erythematosus (SLE) and their link to lupus nephritis 145 SLE. A total of 145 healthy controls were subjected to clinical and laboratory evaluation. The disease activity was assessed by the SLE disease activity index (SLEDAI) score. SLE patients were divided into two subgroups according to the presence of lupus nephritis. The TUG1 gene polymorphisms rs5749201 and rs886471 were determined by Sanger sequencing, and TUG1 expression was assessed by qRT-PCR. There was a significant increase in the risk of SLE AA, TA, dominant genotypes, and the A allele of rs5749201 (p < 0.001) by 4.9-, 10.1-, 6.5-, and 2.5-fold in comparison to the relative control. GG and TG, dominant genotypes and the G allele of rs886471 (p < 0.01) increased the risk by 5.09-, 11.9-, 6.5-, and 2.6-fold. AA, A allele, dominant and recessive rs5749201genotypes increased the risk of lupus nephritis by 16.6-, 7.4-, 7.1-, and 12.2-fold, respectively (p < 0.05). GG, dominant and recessive genotypes, and the G allele of rs886471 increased the risk of lupus nephritis by 17.04-, 7.8-, 9.4-, and 6.08-fold, respectively (p < 0.05). Additionally, the AG haplotype increased the risk of SLE and lupus nephritis by 2.7- and 7.8-fold, respectively. The AA rs5749201 and GG rs886471 variants are significantly associated with more severe disease (p < 0.001). TUG1 expression was significantly higher in SLE than in the control and in the lupus nephritis than in non-lupus nephritis cases (p < 0.05). Interestingly, AA rs5749201 and GG rs886471 were significantly associated with higher TUG1 levels (p < 0.001). It was also found that AA rs5749201 and high SLEDAI were predictors of lupus nephritis. Overall, our findings illustrated for the first time that TUG1 gene rs5749201 and rs886471 variants were associated with increased risk of SLE, more severe disease, and lupus nephritis, and the TUG1 level could be used as a diagnostic biomarker of SLE and lupus nephritis.

Project description:Background:Long noncoding RNAs (lncRNAs) are emerging as critical regulators of gene expression in the immune system, but their impact on neuropsychiatric systemic lupus erythematosus (NPSLE) remains unknown. Methods:RNA sequencing analysis was used to screen the comprehensive expression profile of lncRNAs and messenger RNAs (mRNAs) in peripheral blood mononuclear cells (PBMCs) from NPSLE patients, active SLE patients who had never experienced neuropsychiatric manifestations (Non-NPSLE) and healthy controls. Differentially expressed (DE) lncRNA levels were validated by qRT-PCR in 26 NPSLE patients, 31 Non-NPSLE patients and 30 healthy controls. Further, correlations of DE lncRNAs with clinical manifestations of NPSLE patients were analyzed. Finally, a bioinformatic analysis was performed to investigate the potential functions of DE genes. Results:Four hundred and fifty-one lncRNAs and 272 mRNAs were DE between the NPSLE patients and Non-NPSLE patients, among which, significantly upregulated expression levels of NONHSAT208182.1, NONHSAT182114.1, NONHSAT106801.2, NONHSAT039491.2, ENST00000356215, NONHSAT087499.2 and NONHSAT207026.1 while downregulated expression levels of NONHSAT001281.2 and NONHSAT024353.2 were further validated in PBMCs from NPSLE patients by qRT-PCR. Bioinformatic analysis suggested several gene ontology (GO) terms and signal pathways may play important roles in NPSLE development. Co-expression networks analysis indicated that 170 lncRNAs and 46 mRNAs were included in the co-expression network. The expression level of NONHSAT039491.2 was associated with the activity of SLE and the presence of anti-dsDNA, anti-RNP antibody, dizziness and headache. NONHSAT087499.2 level correlated with anti-RNA antibody, ENST00000356215 level correlated with olfactory threshold and oral ulcer. NONHSAT208182.1 level correlated with the presence of fever, unstable walking and urinary red blood cells. NONHSAT106801.2 correlated with frequency of B cells and the presence of fever. NONHSAT024353.2 level was associated with serum IgG levels and the presence of anti-SSA and disorder of consciousness. Conclusions:Our data provided comprehensive evidence regarding the differential expression of lncRNAs in PBMCs from NPSLE patients, indicating that these DE lncRNAs may play roles in NPSLE development. Our finding shed light on the understanding of the molecular mechanisms of lncRNAs in the pathogenesis of NPSLE.

Project description:BackgroundSystemic lupus erythematosus (SLE) may cause pathogenic changes in the placentas during human pregnancy, such as decreased placental weight, intraplacental hematoma, ischemic hypoxic change, placental infarction, and decidual vasculopathy, which contribute to high maternal and fetal mortality and morbidity. Sex-specific adaptations of the fetus are associated with SLE pregnancies. The present study aimed to determine the transcriptomic profiles of female and male placentas from women with SLE.MethodsRNA sequencing (RNA-seq) was performed to identify differentially expressed protein-coding genes (DEGs) in placentas from women with SLE vs. normal term (NT) pregnancies with female and male fetuses (n = 3-5/sex/group). Real-time-quantitative PCR was performed (n = 4 /sex/group) to validate the RNA-seq results. Bioinformatics functional analysis was performed to predict the biological functions and pathways of SLE-dysregulated protein-coding genes.ResultsCompared with NT-female (NT-F) placentas, 119 DEGs were identified in SLE-female (SLE-F) placentas. Among these 119 DEGs, five and zero are located on X- and Y-chromosomes, respectively, and four are located on the mitochondrial genome. Compared with NT-male (NT-M) placentas, 458 DEGs were identified in SLE-male (SLE-M) placentas, among which 16 are located on the X-chromosome and zero on the Y-chromosome and mitochondrial genome. Twenty-four DEGs were commonly dysregulated in SLE-F and -M placentas. Functional analysis showed that SLE-dysregulated protein-coding genes were associated with diverse biological functions and pathways, including angiogenesis, cellular response to growth factor stimulus, heparin-binding, HIF (hypoxia-inducible factor)-1 signaling pathway, and Interleukin-17 (IL-17) signaling pathway in both SLE-F and -M placentas. Biological regulations were differentially enriched between SLE-F and -M placentas. Regulation of blood circulation, response to glucocorticoid, and rhythmic process were all enriched in SLE-F, but not SLE-M placentas. In contrast, tumor necrosis factor production, Th17 cell differentiation, and MDA (melanoma differentiation-associated gene)-5 signaling pathway were enriched in SLE-M but not SLE-F placentas.ConclusionThis report investigated the protein-coding gene profiles of placenta tissues from SLE patients using RNA-seq. The results suggest that the SLE-dysregulated protein-coding genes in placentas may contribute to the pathophysiological progress of SLE pregnancies in a fetal sex-specific manner, leading to adverse pregnancy outcomes.

Dataset Information

Integrative analysis of long non-coding RNAs and messenger RNA expression profiles in systemic lupus erythematosus.

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Integrative analysis of long non-coding RNAs and messenger RNA expression profiles in systemic lupus erythematosus.

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