Positively correlated miRNA-mRNA regulatory networks in mouse frontal cortex during early stages of alcohol dependence

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dc.creatorNunez, Yury O.en
dc.creatorTruitt, Jay M.en
dc.creatorGorini, Giorgioen
dc.creatorPonomareva, Olga N.en
dc.creatorBlendnoven
dc.creatorHarris, R. Adronen
dc.creatorMayfield, R. Dayneen
dc.date.accessioned2014-12-15T17:10:55Zen
dc.date.available2014-12-15T17:10:55Zen
dc.date.issued2013-10-22en
dc.descriptionYury O Nunez, Jay M Truitt, Giorgio Gorini, Olga N Ponomareva, Yuri A Blednov, R Adron Harris and R Dayne Mayfield are with The Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, USAen
dc.description.abstractBackground: Although the study of gene regulation via the action of specific microRNAs (miRNAs) has experienced a boom in recent years, the analysis of genome-wide interaction networks among miRNAs and respective targeted mRNAs has lagged behind. MicroRNAs simultaneously target many transcripts and fine-tune the expression of genes through cooperative/combinatorial targeting. Therefore, they have a large regulatory potential that could widely impact development and progression of diseases, as well as contribute unpredicted collateral effects due to their natural, pathophysiological, or treatment-induced modulation. We support the viewpoint that whole mirnome-transcriptome interaction analysis is required to better understand the mechanisms and potential consequences of miRNA regulation and/or deregulation in relevant biological models. In this study, we tested the hypotheses that ethanol consumption induces changes in miRNA-mRNA interaction networks in the mouse frontal cortex and that some of the changes observed in the mouse are equivalent to changes in similar brain regions from human alcoholics. Results: miRNA-mRNA interaction networks responding to ethanol insult were identified by differential expression analysis and weighted gene coexpression network analysis (WGCNA). Important pathways (coexpressed modular networks detected by WGCNA) and hub genes central to the neuronal response to ethanol are highlighted, as well as key miRNAs that regulate these processes and therefore represent potential therapeutic targets for treating alcohol addiction. Importantly, we discovered a conserved signature of changing miRNAs between ethanol-treated mice and human alcoholics, which provides a valuable tool for future biomarker/diagnostic studies in humans. We report positively correlated miRNA-mRNA expression networks that suggest an adaptive, targeted miRNA response due to binge ethanol drinking. Conclusions: This study provides new evidence for the role of miRNA regulation in brain homeostasis and sheds new light on current understanding of the development of alcohol dependence. To our knowledge this is the first report that activated expression of miRNAs correlates with activated expression of mRNAs rather than with mRNA downregulation in an in vivo model. We speculate that early activation of miRNAs designed to limit the effects of alcohol-induced genes may be an essential adaptive response during disease progression.en
dc.description.catalogingnotedayne.mayfield@austin.utexas.eduen
dc.description.departmentWaggoner Center for Alcohol and Addiction Researchen
dc.description.sponsorshipen
dc.identifier.Filename1471-2164-14-725.pdfen
dc.identifier.citationNunez, Yury O., Jay M. Truitt, Giorgio Gorini, Olga N. Ponomareva, Yuri A. Blednov, R. A. Harris, and R. D. Mayfield. “Positively Correlated miRNA-mRNA Regulatory Networks in Mouse Frontal Cortex during Early Stages of Alcohol Dependence.” BMC Genomics 14, no. 1 (October 22, 2013): 725. doi:10.1186/1471-2164-14-725.en
dc.identifier.doidoi:10.1186/1471-2164-14-725en
dc.identifier.urihttp://hdl.handle.net/2152/27951en
dc.language.isoEnglishen
dc.publisherBMC Genomicsen
dc.rightsAdministrative deposit of works to UT Digital Repository: This works author(s) is or was a University faculty member, student or staff member; this article is already available through open access at http://www.biomedcentral.com. The public license is specified as CC-BY: http://creativecommons.org/licenses/by/4.0/. The library makes the deposit as a matter of fair use (for scholarly, educational, and research purposes), and to preserve the work and further secure public access to the works of the University.en
dc.subjectmRNAen
dc.subjectmiRNAen
dc.subjectexpression profilingen
dc.subjectWGCNAen
dc.subjectnetwork analysisen
dc.subjectmouseen
dc.subjecthumanen
dc.subjectalcoholismen
dc.subjectalcohol dependenceen
dc.subjectfrontal cortexen
dc.titlePositively correlated miRNA-mRNA regulatory networks in mouse frontal cortex during early stages of alcohol dependenceen
dc.typeArticleen

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