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Expression of disease-related miRNAs in white-matter lesions of progressive multiple sclerosis brains.


ABSTRACT:

Background

MicroRNA (miRNA) expression in the serum of multiple sclerosis (MS) patients has been correlated with white matter (WM) magnetic resonance imaging (MRI) abnormalities. The expression levels and cellular specificity of the target genes of these miRNAs are unknown in MS brain.

Objective

The aim of this study was to analyze and validate the expression of miRNAs, previously reported as dysregulated in sera of MS patients, in white-matter lesions (WMLs) of progressive MS brains.

Methods

We performed global miRNA expression profiling analysis in demyelinated WMLs of progressive MS brains (n = 5) and compared the significantly altered miRNAs to previously identified miRNAs from sera of MS patients. Top dysregulated miRNAs common between the two datasets were validated in an independent cohort of MS brains by quantitative PCR (qPCR) and in situ hybridization.

Results

Among the miRNAs that were significantly changed in WML tissues, 11 were similar to pathogenic and 12 were common to protective miRNAs previously identified in sera and correlating with WM MRI abnormalities. Importantly, the expression levels of 58% of the protective miRNAs (7 of 12) were decreased in MS lesions compared to surrounding normal-appearing tissue. Target genes of these miRNAs were also altered in MS lesions and queries of cell-specific databases identified astrocytes and microglia as the key cellular expressers of these genes in MS brains.

Conclusions

We identified miRNAs that correlate with MRI abnormalities in lesioned tissue from MS brains.

SUBMITTER: Tripathi A 

PROVIDER: S-EPMC6530016 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Expression of disease-related miRNAs in white-matter lesions of progressive multiple sclerosis brains.

Tripathi Ajai A   Volsko Christina C   Datta Ushasi U   Regev Keren K   Dutta Ranjan R  

Annals of clinical and translational neurology 20190321 5


<h4>Background</h4>MicroRNA (miRNA) expression in the serum of multiple sclerosis (MS) patients has been correlated with white matter (WM) magnetic resonance imaging (MRI) abnormalities. The expression levels and cellular specificity of the target genes of these miRNAs are unknown in MS brain.<h4>Objective</h4>The aim of this study was to analyze and validate the expression of miRNAs, previously reported as dysregulated in sera of MS patients, in white-matter lesions (WMLs) of progressive MS bra  ...[more]

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