Dataset Information

Analysis of microRNA and Gene Expression Profiles in Multiple Sclerosis: Integrating Interaction Data to Uncover Regulatory Mechanisms.

ABSTRACT: MicroRNAs (miRNAs) have been reported to contribute to the pathophysiology of multiple sclerosis (MS), an inflammatory disorder of the central nervous system. Here, we propose a new consensus-based strategy to analyse and integrate miRNA and gene expression data in MS as well as other publically available data to gain a deeper understanding of the role of miRNAs in MS and to overcome the challenges posed by studies with limited patient sample sizes. We processed and analysed microarray datasets, and compared the expression of genes and miRNAs in the blood of MS patients and controls. We then used our consensus and integration approach to construct two molecular networks dysregulated in MS: a miRNA- and a gene-based network. We identified 18 differentially expressed (DE) miRNAs and 128 DE genes that may contribute to the regulatory alterations behind MS. The miRNAs were linked to immunological and neurological pathways, and we exposed let-7b-5p and miR-345-5p as promising blood-derived disease biomarkers in MS. The results suggest that DE miRNAs are more informative than DE genes in uncovering pathways potentially involved in MS. Our findings provide novel insights into the regulatory mechanisms and networks underlying MS.

SUBMITTER: Freiesleben S

PROVIDER: S-EPMC5046091 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Publications

Analysis of microRNA and Gene Expression Profiles in Multiple Sclerosis: Integrating Interaction Data to Uncover Regulatory Mechanisms.

Freiesleben Sherry S Hecker Michael M Zettl Uwe Klaus UK Fuellen Georg G Taher Leila L

Scientific reports 20161003

MicroRNAs (miRNAs) have been reported to contribute to the pathophysiology of multiple sclerosis (MS), an inflammatory disorder of the central nervous system. Here, we propose a new consensus-based strategy to analyse and integrate miRNA and gene expression data in MS as well as other publically available data to gain a deeper understanding of the role of miRNAs in MS and to overcome the challenges posed by studies with limited patient sample sizes. We processed and analysed microarray datasets, ...[more]

PMID: 27694855

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Project description:MicroRNAs (miRNAs) have been reported to contribute to the pathophysiology of the Parkinson's disease (PD), an age related-neurodegenerative disorder. The aim of present study was to compare the expression profiles of a new set of candidate miRNAs related to aging and cellular senescence in peripheral blood mononuclear cells (PBMCs) obtained from the PD patients with healthy controls and then in the early and advanced stages of the PD patients with their controls to clarify whether their expression was correlated with the disease severity. We have also proposed a consensus-based strategy to interpret the miRNAs expression data to gain a better insight into the molecular regulatory alterations during the incidence of PD. We evaluated the miRNA expression levels in the PBMCs obtained from 36 patients with PD and 16 healthy controls by the reverse transcription-quantitative real-time PCR and their performance to discriminate the PD patients from the healthy subjects assessed using the receiver operating characteristic curve analysis. Also, we applied our consensus and integration approach to construct a deregulated miRNA-based network in PD with the respective targets and transcription factors, and the enriched gene ontology and pathways using the enrichment analysis approach were obtained. There was a significant overexpression of miR-885 and miR-17 and the downregulation of miR-361 in the PD patients compared to the controls. The blood expression of miR-885 and miR-17 tended to increase along with the disease severity. On the other hand, the lower levels of miR-361 in the early stages of the PD patients, as compared to controls, and its higher levels in the advanced stages of PD patients, as compared to the early stages of the PD patients, were observed. Combination of all three miRNAs showed an appropriate value of AUC (0.985) to discriminate the PD patients from the healthy subjects. Also, the deregulated miRNAs were linked to the known PD pathways and the candidate related target genes were presented. We revealed 3 candidate biomarkers related to aging and cellular senescence for the first time in the patients with PD. Our in-silico analysis identified candidate target genes and TFs, including those related to neurodegeneration and PD. Overall, our findings provided novel insights into the probable age-regulatory mechanisms underlying PD and a rationale to further clarify the role of the identified miRNAs in the PD pathogenesis.

Dataset Information

Analysis of microRNA and Gene Expression Profiles in Multiple Sclerosis: Integrating Interaction Data to Uncover Regulatory Mechanisms.

Publications

Analysis of microRNA and Gene Expression Profiles in Multiple Sclerosis: Integrating Interaction Data to Uncover Regulatory Mechanisms.

Similar Datasets

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