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The potential roles of long non-coding RNAs in lipopolysaccharide-induced human peripheral blood mononuclear cells as determined by microarray analysis.

ABSTRACT: Sepsis arises from an aberrant and excessive host response to infection. Long noncoding RNAs (lncRNAs) are involved in multiple cellular functions, including inflammation and immunity. However, to date there has been no systematic attempt to identify lncRNAs whose expression is changed after the induction of the innate immune response. In this study, we profiled global lncRNA and mRNA expression changes in peripheral blood mononuclear cells (PBMCs) treated with lipopolysaccharide (LPS) using a microarray platform. Of the 40 914 lncRNAs screened, 596 were significantly upregulated and 250 were significantly downregulated (corrected P < 0.05) in response to LPS. Of the 34 236 mRNAs screened, 802 were upregulated and 549 were downregulated. Functional annotation analysis indicated that lncRNA-associated differentially expressed mRNAs were primarily enriched in host immune and inflammatory responses. This study provides the first lncRNA and mRNA transcriptomic landscape of LPS-mediated changes in human PBMCs. These findings may provide potential insights into lncRNAs involved in the immunopathology of sepsis.

SUBMITTER: Zhang A

PROVIDER: S-EPMC6325599 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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The potential roles of long non-coding RNAs in lipopolysaccharide-induced human peripheral blood mononuclear cells as determined by microarray analysis.

Zhang Anqiang A Lu Hongxiang H Wen Dalin D Sun Jianhui J Du Juan J Wang Xu X Gu Wei W Jiang Jianxin J

FEBS open bio 20181225 1

Sepsis arises from an aberrant and excessive host response to infection. Long noncoding RNAs (lncRNAs) are involved in multiple cellular functions, including inflammation and immunity. However, to date there has been no systematic attempt to identify lncRNAs whose expression is changed after the induction of the innate immune response. In this study, we profiled global lncRNA and mRNA expression changes in peripheral blood mononuclear cells (PBMCs) treated with lipopolysaccharide (LPS) using a m ...[more]

PMID: 30652082

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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:BackgroundCircular RNA (circRNA) is a type of closed circular noncoding RNA (ncRNA), mostly formed by back-splicing or alternative splicing of pre-messenger RNA (mRNA). The aim of this study was to explore the expression profile of circRNA in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS) and discover potential molecular markers of AS.MethodsThe circRNA microarray technology was used to detect the expression of circRNAs in the peripheral blood of 6 patients with AS and 6 healthy controls (HC). To screen the differentially expressed circRNAs by fold change (FC) and P value, these differentially expressed circRNAs were analyzed by bioinformatics. In 60 cases of AS and 30 cases of HC, 4 circRNAs were subjected to real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), and their correlation with various clinical indicators was analyzed. Finally, the receiver operating characteristic (ROC) curve was used to analyze their potential as AS diagnostic markers.ResultsThe microarray results showed that there were 1369 significantly differently expressed (P < 0.05, FC > 1.5) circRNAs between the AS and HC groups (675 upregulated and 694 downregulated). The results of bioinformatics analysis suggested that they were mainly involved in "enzyme binding," "adenosine ribonucleotide binding," "MAPK signaling pathway", etc. The RT-qPCR results showed that the expressions of hsa_circRNA_001544 (U = 486.5, P < 0.05) and hsa_circRNA_102532 (U = 645, P < 0.05) were significantly different between the AS group and the HC group. The AS group was further divided into two subgroups: active AS (ASA) and stable AS (ASS). After analysis, it was found that compared with the HC group, hsa_circRNA_001544 was significantly increased in both ASA (U = 214, P < 0.05) and ASS groups (U = 273, P < 0.05), while hsa_circRNA_008961 (U = 250, P < 0.05) and hsa_circRNA_102532 (U = 295, P < 0.05) were only significantly increased in the ASA group. Furthermore, hsa_circRNA_012732 was significantly different between the ASA and ASS groups (U = 194, P < 0.05), and there was no statistical significance among the remaining groups. Correlation analysis results showed that hsa_circRNA_012732 was negatively correlated with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), high-sensitivity C-reactive protein (hsCRP), and globulin (GLOB) and positively correlated with lymphocyte count (LY), mean corpusular volume, and albumin (ALB), and hsa_circRNA_008961 was negatively correlated with platelet (PLT) count. ROC curve analysis showed that hsa_circRNA_001544 (95% CI = 0.610-0.831, P < 0.05) and hsa_circRNA_102532 (95% CI = 0.521-0.762, P < 0.05) were statistically significant, and their area under curve (AUC) values were 0.720 and 0.642, respectively.ConclusionsThere are differentially expressed circRNAs in PBMCs of AS patients, and they may be involved in the occurrence and development of AS. Among these differentially expressed circRNAs, hsa_circRNA_012732 has the potential to become an indicator of disease activity, and hsa_circRNA_001544 has the potential to become a molecular marker for AS diagnosis.

Dataset Information

The potential roles of long non-coding RNAs in lipopolysaccharide-induced human peripheral blood mononuclear cells as determined by microarray analysis.

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The potential roles of long non-coding RNAs in lipopolysaccharide-induced human peripheral blood mononuclear cells as determined by microarray analysis.

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