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A miRNA signature of prion induced neurodegeneration.
PLoS One. 2008; 3(11):e3652.Plos

Abstract

MicroRNAs (miRNAs) are small, non-coding RNA molecules which are emerging as key regulators of numerous cellular processes. Compelling evidence links miRNAs to the control of neuronal development and differentiation, however, little is known about their role in neurodegeneration. We used microarrays and RT-PCR to profile miRNA expression changes in the brains of mice infected with mouse-adapted scrapie. We determined 15 miRNAs were de-regulated during the disease processes; miR-342-3p, miR-320, let-7b, miR-328, miR-128, miR-139-5p and miR-146a were over 2.5 fold up-regulated and miR-338-3p and miR-337-3p over 2.5 fold down-regulated. Only one of these miRNAs, miR-128, has previously been shown to be de-regulated in neurodegenerative disease. De-regulation of a unique subset of miRNAs suggests a conserved, disease-specific pattern of differentially expressed miRNAs is associated with prion-induced neurodegeneration. Computational analysis predicted numerous potential gene targets of these miRNAs, including 119 genes previously determined to be also de-regulated in mouse scrapie. We used a co-ordinated approach to integrate miRNA and mRNA profiling, bioinformatic predictions and biochemical validation to determine miRNA regulated processes and genes potentially involved in disease progression. In particular, a correlation between miRNA expression and putative gene targets involved in intracellular protein-degradation pathways and signaling pathways related to cell death, synapse function and neurogenesis was identified.

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Authors+Show Affiliations

Saba R
Molecular PathoBiology, National Microbiology Laboratory, Canadian Science Center for Human and Animal Health, Public Health Agency of Canada, Winnipeg, Canada.
Goodman CD
No affiliation info available
Huzarewich RL
No affiliation info available
Robertson C
No affiliation info available
Booth SA
No affiliation info available

MeSH

AnimalsBrain ChemistryGene Expression ProfilingGene Expression RegulationGene Regulatory NetworksGenes, ReporterMiceMicroRNAsNerve DegenerationOligonucleotide Array Sequence AnalysisPromoter Regions, GeneticScrapie

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18987751

Citation

Saba, Reuben, et al. "A miRNA Signature of Prion Induced Neurodegeneration." PloS One, vol. 3, no. 11, 2008, pp. e3652.
Saba R, Goodman CD, Huzarewich RL, et al. A miRNA signature of prion induced neurodegeneration. PLoS One. 2008;3(11):e3652.
Saba, R., Goodman, C. D., Huzarewich, R. L., Robertson, C., & Booth, S. A. (2008). A miRNA signature of prion induced neurodegeneration. PloS One, 3(11), e3652. https://doi.org/10.1371/journal.pone.0003652
Saba R, et al. A miRNA Signature of Prion Induced Neurodegeneration. PLoS One. 2008;3(11):e3652. PubMed PMID: 18987751.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A miRNA signature of prion induced neurodegeneration. AU - Saba,Reuben, AU - Goodman,Chelsey D, AU - Huzarewich,Rhiannon L C H, AU - Robertson,Catherine, AU - Booth,Stephanie A, Y1 - 2008/11/06/ PY - 2008/08/01/received PY - 2008/10/03/accepted PY - 2008/11/7/pubmed PY - 2008/12/19/medline PY - 2008/11/7/entrez SP - e3652 EP - e3652 JF - PloS one JO - PLoS One VL - 3 IS - 11 N2 - MicroRNAs (miRNAs) are small, non-coding RNA molecules which are emerging as key regulators of numerous cellular processes. Compelling evidence links miRNAs to the control of neuronal development and differentiation, however, little is known about their role in neurodegeneration. We used microarrays and RT-PCR to profile miRNA expression changes in the brains of mice infected with mouse-adapted scrapie. We determined 15 miRNAs were de-regulated during the disease processes; miR-342-3p, miR-320, let-7b, miR-328, miR-128, miR-139-5p and miR-146a were over 2.5 fold up-regulated and miR-338-3p and miR-337-3p over 2.5 fold down-regulated. Only one of these miRNAs, miR-128, has previously been shown to be de-regulated in neurodegenerative disease. De-regulation of a unique subset of miRNAs suggests a conserved, disease-specific pattern of differentially expressed miRNAs is associated with prion-induced neurodegeneration. Computational analysis predicted numerous potential gene targets of these miRNAs, including 119 genes previously determined to be also de-regulated in mouse scrapie. We used a co-ordinated approach to integrate miRNA and mRNA profiling, bioinformatic predictions and biochemical validation to determine miRNA regulated processes and genes potentially involved in disease progression. In particular, a correlation between miRNA expression and putative gene targets involved in intracellular protein-degradation pathways and signaling pathways related to cell death, synapse function and neurogenesis was identified. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/18987751/A_miRNA_signature_of_prion_induced_neurodegeneration_ L2 - https://dx.plos.org/10.1371/journal.pone.0003652 DB - PRIME DP - Unbound Medicine ER -