Dataset Information

Long non-coding RNA deep sequencing reveals the role of macrophage in liver disorders.

ABSTRACT: Liver disorders such as hepatitis, cirrhosis and hepatocellular carcinoma are a series of the most life threatening diseases along with extensive inflammatory cellular infiltrations. Macrophage has been proved to be key regulators and initiators of inflammation, and long non-coding RNAs (lncRNAs) are recommended to play critical roles in the occurrence and development of a variety of diseases. To uncover the role of macrophage in liver disorders via lncRNA sequencing method, we first applied a lncRNA classification pipeline to identify 1247 lncRNAs represented on the Affymetrix Mouse Genome 430/430A 2.0 array. We then analyzed the lncRNA expression patterns in a set of previously published gene expression profiles of silica particle exposed macrophages and liver respectively, and identified and validated sets of differentially expressed lncRNAs shared by macrophages and liver. The functional enrichment analysis of these lncRNAs was processed on the basis of their expression signatures, three aspects including cis, trans and co-acting proteins were proposed. This is the first time to correlate macrophage with liver disorders via co-expressed lncRNAs. Our findings indicated that roles of macrophage in liver disorders were double-edged, the differentially expressed lncRNAs and their corresponding regulatory genes or proteins may serve as potential diagnostic biomarkers and therapeutic targets.

SUBMITTER: Lin Z

PROVIDER: S-EPMC5777746 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Long non-coding RNA deep sequencing reveals the role of macrophage in liver disorders.

Lin Zhang Z Changfu Hao H Fengling Zhao Z Wei Guo G Lei Bao B Yiping Li L Miao Zhang Z Zhongzheng Yue Y Youliang Zhao Z Shuyin Duan D Wu Yao Y

Oncotarget 20171212 70

Liver disorders such as hepatitis, cirrhosis and hepatocellular carcinoma are a series of the most life threatening diseases along with extensive inflammatory cellular infiltrations. Macrophage has been proved to be key regulators and initiators of inflammation, and long non-coding RNAs (lncRNAs) are recommended to play critical roles in the occurrence and development of a variety of diseases. To uncover the role of macrophage in liver disorders via lncRNA sequencing method, we first applied a l ...[more]

PMID: 29383134

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Project description:BACKGROUND:Sustained and dysfunctional macrophage activation promotes inflammatory cardiometabolic disorders, but the role of long intergenic noncoding RNA (lincRNA) in human macrophage activation and cardiometabolic disorders is poorly defined. Through transcriptomics, bioinformatics, and selective functional studies, we sought to elucidate the lincRNA landscape of human macrophages. METHODS AND RESULTS:We used deep RNA sequencing to assemble the lincRNA transcriptome of human monocyte-derived macrophages at rest and following stimulation with lipopolysaccharide and IFN-? (interferon ?) for M1 activation and IL-4 (interleukin 4) for M2 activation. Through de novo assembly, we identified 2766 macrophage lincRNAs, including 861 that were previously unannotated. The majority (?85%) was nonsyntenic or was syntenic but not annotated as expressed in mouse. Many macrophage lincRNAs demonstrated tissue-enriched transcription patterns (21.5%) and enhancer-like chromatin signatures (60.9%). Macrophage activation, particularly to the M1 phenotype, markedly altered the lincRNA expression profiles, revealing 96 lincRNAs differentially expressed, suggesting potential roles in regulating macrophage inflammatory functions. A subset of lincRNAs overlapped genomewide association study loci for cardiometabolic disorders. MacORIS (macrophage-enriched obesity-associated lincRNA serving as a repressor of IFN-? signaling), a macrophage-enriched lincRNA not expressed in mouse macrophages, harbors variants associated with central obesity. Knockdown of MacORIS, which is located in the cytoplasm, enhanced IFN-?-induced JAK2 (Janus kinase 2) and STAT1 (signal transducer and activator of transcription 1) phosphorylation in THP-1 macrophages, suggesting a potential role as a repressor of IFN-? signaling. Induced pluripotent stem cell-derived macrophages recapitulated the lincRNA transcriptome of human monocyte-derived macrophages and provided a high-fidelity model with which to study lincRNAs in human macrophage biology, particularly those not conserved in mouse. CONCLUSIONS:High-resolution transcriptomics identified lincRNAs that form part of the coordinated response during macrophage activation, including specific macrophage lincRNAs associated with human cardiometabolic disorders that modulate macrophage inflammatory functions.

Dataset Information

Long non-coding RNA deep sequencing reveals the role of macrophage in liver disorders.

Publications

Long non-coding RNA deep sequencing reveals the role of macrophage in liver disorders.

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