Dataset Information

Bioinformatic analysis of microRNA expression in Huntington's disease.

ABSTRACT: Huntington's disease (HD) is an inherited, progressive neurodegenerative disease caused by a CAG expansion in the Huntingtin (HTT) gene and various dysfunctions of biological processes in HD have been proposed. Although monogenic, the exact pathogenesis of HD currently remains unclear. To identify the synergistic microRNA (miRNA) pattern in HD, the miRNA expression profile dataset GSE64977 and the gene expression profile dataset GSE64810 were downloaded. Programming software R was used to identify differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs). Target genes of DEMs were predicted using the TargetScan database. Gene ontology (GO) function of DEGs was generated using the FunRich and a miRNA?mRNA interaction network was constructed using Cytoscape software. In total, 1,612 DEGs and 10 DEMs were identified. GO terms mainly included inflammatory response and immune response in DEGs. A total of 745 target genes were predicted from the DEMs and 33 overlaps were identified between these target genes and DEGs. The miRNA network demonstrated that hsa?miR?4488, hsa?miR?196a?5p, and hsa?miR?549a had a high degree and may be involved with the pathogenesis and potential therapeutic targets of HD.

SUBMITTER: Dong X

PROVIDER: S-EPMC6102687 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Bioinformatic analysis of microRNA expression in Huntington's disease.

Dong Xiaoyu X Cong Shuyan S

Molecular medicine reports 20180629 3

Huntington's disease (HD) is an inherited, progressive neurodegenerative disease caused by a CAG expansion in the Huntingtin (HTT) gene and various dysfunctions of biological processes in HD have been proposed. Although monogenic, the exact pathogenesis of HD currently remains unclear. To identify the synergistic microRNA (miRNA) pattern in HD, the miRNA expression profile dataset GSE64977 and the gene expression profile dataset GSE64810 were downloaded. Programming software R was used to identi ...[more]

PMID: 30015953

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Project description:Objective: MicroRNAs (miRNAs) in exosomes had been implicated differentially expressed in patient with moyamoya disease (MMD), but the miRNAs expression in circulating leukocytes remains unclear. This study was investigated on the differential expression of miRNAs in peripheral leukocytes between MMD patients and healthy adults, and among patients with subtypes of MMD. Materials and methods: A total of 30 patients with MMD and 10 healthy adults were enrolled in a stroke center from October 2017 to December 2018. The gene microarray was used to detect the differential expression profiles of miRNA in leukocytes between MMD patients and controls, and the differentially expressed miRNAs were verified by the method of real-time PCR. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to explore the key signaling pathways and possible pathogenesis of MMD. Results: The microarray results showed 12 differentially expressed miRNAs in leukocytes of MMD patients compared with controls (fold change >2.0, p < 0.05 and FDR <0.05), of which 8 miRNAs were upregulated (miRNA-142-5p, miRNA-29b-3p, miRNA-424-5p, MiRNA-582-5p, miRNA-6807-5p, miRNA-142-3p, miRNA-340-5p, miRNA-4270), and 4 miRNAs were downregulated (miRNA-144-3p, miRNA-451a, miRNA-486-5p, miRNA-363-3p). The real-time PCR confirmed seven differentially expressed miRNAs (p < 0.05), of which 4 miRNAs (miRNA-29b-3p, miRNA-142-3p, miRNA-340-5p, miRNA-582-5p) were upregulated, and 3 miRNAs (miRNA-363-3p, miRNA-451a and miRNA-486-5p) were downregulated. Both GO and KEGG analysis suggested that the Wnt signaling pathway may be involved in the pathogenesis of MMD. In addition, miRNAs were also differentially expressed among patients with subtypes of MMD. Conclusion: This study indicated that miRNAs are differentially expressed in peripheral leukocytes between MMD patients and healthy adults, and among patients with subtypes of MMD. The Wnt signaling pathway is probably involved in the pathogenesis of MMD.

Project description:BackgroundHuntington's disease (HD) is a neurodegenerative disorder characterized by psychiatric symptoms, serious motor and cognitive deficits. Certain pathological changes can already be observed in pre-symptomatic HD (pre-HD) patients; however, the underlying molecular pathogenesis is still uncertain and no effective treatments are available until now. Here, we reanalyzed HD-related differentially expressed genes from the GEO database between symptomatic HD patients, pre-HD individuals, and healthy controls using bioinformatics analysis, hoping to get more insight in the pathogenesis of both pre-HD and HD, and shed a light in the potential therapeutic targets of the disease.MethodsPre-HD and symptomatic HD differentially expressed genes (DEGs) were screened by bioinformatics analysis Gene Expression Omnibus (GEO) dataset GSE1751. A protein-protein interaction (PPI) network was used to select hub genes. Subsequently, Gene Ontology (GO) enrichment analysis of DEGs and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of hub genes were applied. Dataset GSE24250 was downloaded to verify our hub genes by the Kaplan-Meier method using Graphpad Prism 5.0. Finally, target miRNAs of intersected hub genes involved in pre-HD and symptomatic HD were predicted.ResultsA total of 37 and 985 DEGs were identified in pre-HD and symptomatic HD, respectively. The hub genes, SIRT1, SUZ12, and PSMC6, may be implicated in pre-HD, and the hub genes, FIS1, SIRT1, CCNH, SUZ12, and 10 others, may be implicated in symptomatic HD. The intersected hub genes, SIRT1 and SUZ12, and their predicted target miRNAs, in particular miR-22-3p and miR-19b, may be significantly associated with pre-HD.ConclusionThe PSMC6, SIRT1, and SUZ12 genes and their related ubiquitin-mediated proteolysis, transcriptional dysregulation, and histone metabolism are significantly associated with pre-HD. FIS1, CCNH, and their related mitochondrial disruption and transcriptional dysregulation processes are related to symptomatic HD, which might shed a light on the elucidation of potential therapeutic targets in HD.

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Project description:BackgroundHuntington's disease (HD) is a devastating brain disorder with no effective treatment or cure available. The scarcity of brain tissue makes it hard to study changes in the brain and impossible to perform longitudinal studies. However, peripheral pathology in HD suggests that it is possible to study the disease using peripheral tissue as a monitoring tool for disease progression and/or efficacy of novel therapies. In this study, we investigated if blood can be used to monitor disease severity and progression in brain. Since previous attempts using only gene expression proved unsuccessful, we compared blood and brain Huntington's disease signatures in a functional context.MethodsMicroarray HD gene expression profiles from three brain regions were compared to the transcriptome of HD blood generated by next generation sequencing. The comparison was performed with a combination of weighted gene co-expression network analysis and literature based functional analysis (Concept Profile Analysis). Uniquely, our comparison of blood and brain datasets was not based on (the very limited) gene overlap but on the similarity between the gene annotations in four different semantic categories: "biological process", "cellular component", "molecular function" and "disease or syndrome".ResultsWe identified signatures in HD blood reflecting a broad pathophysiological spectrum, including alterations in the immune response, sphingolipid biosynthetic processes, lipid transport, cell signaling, protein modification, spliceosome, RNA splicing, vesicle transport, cell signaling and synaptic transmission. Part of this spectrum was reminiscent of the brain pathology. The HD signatures in caudate nucleus and BA4 exhibited the highest similarity with blood, irrespective of the category of semantic annotations used. BA9 exhibited an intermediate similarity, while cerebellum had the least similarity. We present two signatures that were shared between blood and brain: immune response and spinocerebellar ataxias.ConclusionsOur results demonstrate that HD blood exhibits dysregulation that is similar to brain at a functional level, but not necessarily at the level of individual genes. We report two common signatures that can be used to monitor the pathology in brain of HD patients in a non-invasive manner. Our results are an exemplar of how signals in blood data can be used to represent brain disorders. Our methodology can be used to study disease specific signatures in diseases where heterogeneous tissues are involved in the pathology.

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Bioinformatic analysis of microRNA expression in Huntington's disease.

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Bioinformatic analysis of microRNA expression in Huntington's disease.

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