Document Detail


Over-expression of the miRNA cluster at chromosome 14q32 in the alcoholic brain correlates with suppression of predicted target mRNA required for oligodendrocyte proliferation.
MedLine Citation:
PMID:  23747354     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We examined miRNA expression from RNA isolated from the frontal cortex (Broadman area 9) of 9 alcoholics (6 males, 3 females, mean age 48 years) and 9 matched controls using both the Affymetrix GeneChip miRNA 2.0 and Human Exon 1.0 ST Arrays to further characterize genetic influences in alcoholism and the effects of alcohol consumption on predicted target mRNA expression. A total of 12 human miRNAs were significantly up-regulated in alcohol dependent subjects (fold change≥1.5, false discovery rate (FDR)≤0.3; p<0.05) compared with controls including a cluster of 4 miRNAs (e.g., miR-377, miR-379) from the maternally expressed 14q32 chromosome region. The status of the up-regulated miRNAs was supported using the high-throughput method of exon microarrays showing decreased predicted mRNA gene target expression as anticipated from the same RNA aliquot. Predicted mRNA targets were involved in cellular adhesion (e.g., THBS2), tissue differentiation (e.g., CHN2), neuronal migration (e.g., NDE1), myelination (e.g., UGT8, CNP) and oligodendrocyte proliferation (e.g., ENPP2, SEMA4D1). Our data support an association of alcoholism with up-regulation of a cluster of miRNAs located in the genomic imprinted domain on chromosome 14q32 with their predicted gene targets involved with oligodendrocyte growth, differentiation and signaling.
Authors:
A M Manzardo; S Gunewardena; M G Butler
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-06-06
Journal Detail:
Title:  Gene     Volume:  526     ISSN:  1879-0038     ISO Abbreviation:  Gene     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-07-29     Completed Date:  2013-10-18     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  7706761     Medline TA:  Gene     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  356-63     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Elsevier B.V. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Adult
Alcoholism / genetics*
Brain / metabolism*
Cell Proliferation
Chromosomes, Human, Pair 14*
Cluster Analysis
Exons
Female
Gene Expression*
Gene Expression Profiling
Gene Expression Regulation
Humans
Male
MicroRNAs / genetics*,  metabolism
Middle Aged
Multigene Family*
Oligodendroglia / metabolism*
RNA, Messenger / genetics*,  metabolism
Grant Support
ID/Acronym/Agency:
HD02528/HD/NICHD NIH HHS; K01 AA015935/AA/NIAAA NIH HHS; K01-AA015935/AA/NIAAA NIH HHS; R24AA012725/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/MicroRNAs; 0/RNA, Messenger
Comments/Corrections

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