Dataset Information

Integrated analysis of lncRNA, miRNA and mRNA expression profiling in patients with systemic lupus erythematosus.

ABSTRACT:

Introduction

A great deal of research has reported dysregulated expression of genes in systemic lupus erythematosus (SLE). This study aimed to analyze the lncRNA, miRNA and mRNA expression profile in SLE.

Material and methods

RNA sequencing (RNA-seq) was used to detect the dysregulated RNAs in SLE. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were used to explore the function of these differentially expressed RNAs.

Results

2,353 lncRNAs, 827 mRNAs and 24 miRNAs were shown to be differentially expressed. GO analyses demonstrated that differentially expressed RNAs were enriched in a variety of molecular functions and biological processes including ribonucleotide, protein serine/threonine kinase activity function, regulation of B cell differentiation and others. KEGG pathway analyses revealed that differentially expressed mRNAs and lncRNAs were both enriched in Fc?R-mediated phagocytosis, glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate and glyoxylate and dicarboxylate metabolism pathways. The up-regulated miRNAs target genes were mainly enriched in the nuclear factor-?B (NF-?B) signaling pathway. The down-regulated miRNAs target genes were significantly enriched in metabolism of xenobiotics by cytochrome P450, bile secretion and terpenoid backbone biosynthesis pathways.

Conclusions

The current study reveals a comprehensive expression profile of lncRNAs, miRNAs and mRNAs and implies potential regulatory functions of these RNAs which are involved in the pathogenesis of SLE.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC6657242 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Integrated analysis of lncRNA, miRNA and mRNA expression profiling in patients with systemic lupus erythematosus.

Zhang Qin Q Liang Yan Y Yuan Hui H Li Si S Wang Jie-Bing JB Li Xiao-Mei XM Tao Jin-Hui JH Pan Hai-Feng HF Ye Dong-Qing DQ

Archives of medical science : AMS 20181019 4

<h4>Introduction</h4>A great deal of research has reported dysregulated expression of genes in systemic lupus erythematosus (SLE). This study aimed to analyze the lncRNA, miRNA and mRNA expression profile in SLE.<h4>Material and methods</h4>RNA sequencing (RNA-seq) was used to detect the dysregulated RNAs in SLE. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were used to explore the function of these differentially expressed RNAs.<h4>Results</h4>2,353 ln ...[more]

PMID: 31360182

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Project description:ObjectivesTo investigate the immune cell profiles of patients with systemic lupus erythematosus (SLE), and to identify longitudinal changes in those profiles over time.MethodsWe employed mass cytometry with 3 different panels of 38-39 markers (an immunophenotyping panel, a T cell/monocyte panel, and a B cell panel) in cryopreserved peripheral blood mononuclear cells (PBMCs) from 9 patients with early SLE, 15 patients with established SLE, and 14 controls without autoimmune disease. We used machine learning-driven clustering, flow self-organizing maps, and dimensional reduction with t-distributed stochastic neighbor embedding to identify unique cell populations in early SLE and established SLE. We used mass cytometry data of PBMCs from 19 patients with early rheumatoid arthritis (RA) and 23 controls to compare levels of specific cell populations in early RA and SLE. For the 9 patients with early SLE, longitudinal mass cytometry analysis was applied to PBMCs at enrollment, 6 months after enrollment, and 1 year after enrollment. Serum samples were also assayed for 65 cytokines using Luminex multiplex assay, and associations between cell types and cytokines/chemokines were assessed.ResultsLevels of peripheral helper T cells, follicular helper T (Tfh) cells, and several Ki-67+ proliferating subsets (ICOS+Ki-67+ CD8 T cells, Ki-67+ regulatory T cells, CD19intermediate Ki-67high plasmablasts, and PU.1high Ki-67high monocytes) were increased in patients with early SLE, with more prominent alterations than were seen in patients with early RA. Longitudinal mass cytometry and multiplex serum cytokine assays of samples from patients with early SLE revealed that levels of Tfh cells and CXCL10 had decreased 1 year after enrollment. Levels of CXCL13 were positively correlated with levels of several of the expanded cell populations in early SLE.ConclusionTwo major helper T cell subsets and unique Ki-67+ proliferating immune cell subsets were expanded in patients in the early phase of SLE, and the immunologic features characteristic of early SLE evolved over time.

Project description:BackgroundUlcerative colitis (UC) is associated with differential colonic expression of genes involved in immune response (e.g. IL8) and barrier integrity (e.g. cadherins). MicroRNAs (miRNAs) are regulators of gene expression and are involved in various immune-related diseases. In this study, we investigated (1) if miRNA expression in UC mucosa is altered and (2) if any of these changes correlate with mucosal mRNA expression. Integration of mRNA and miRNA expression profiling may allow the identification of functional links between dysregulated miRNAs and their target mRNA.MethodologyColonic mucosal biopsies were obtained from 17 UC (10 active and 7 inactive) patients and 10 normal controls. Total RNA was used to analyze miRNA and mRNA expression via Affymetrix miRNA 2.0 and Affymetrix Human Gene 1.0ST arrays, respectively. Both miRNA and gene expression profiles were integrated by correlation analysis to identify dysregulated miRNAs with their corresponding predicted target mRNA. Microarray data were validated with qRT-PCR. Regulation of IL8 and CDH11 expression by hsa-miR-200c-3p was determined by luciferase reporter assays.ResultsWhen comparing active UC patients vs. controls, 51 miRNAs and 1543 gene probe sets gave significantly different signals. In contrast, in inactive UC vs. controls, no significant miRNA expression differences were found while 155 gene probe sets had significantly different signals. We then identified potential target genes of the significantly dysregulated miRNAs and genes in active UC vs. controls and found a highly significant inverse correlation between hsa-miR-200c-3p and IL8, an inflammatory marker, and between hsa-miR-200c-3p and CDH11, a gene related to intestinal epithelial barrier function. We could demonstrate that hsa-miR-200c-3p directly regulates IL8 and CDH11 expression.ConclusionDifferential expression of immune- and barrier-related genes in inflamed UC mucosa may be influenced by altered expression of miRNAs. Integrated analysis of miRNA and mRNA expression profiles revealed hsa-miR-200c-3p for use of miRNA mimics as therapeutics.

Dataset Information

Integrated analysis of lncRNA, miRNA and mRNA expression profiling in patients with systemic lupus erythematosus.

Introduction

Material and methods

Results

Conclusions

Publications

Integrated analysis of lncRNA, miRNA and mRNA expression profiling in patients with systemic lupus erythematosus.

Similar Datasets

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