Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5906415 | Gene | 2013 | 8 Pages |
Abstract
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 â¥Â 1.5, false discovery rate (FDR) â¤Â 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.
Keywords
Robust Multichip AveragesnoRNANICHDUPGMART-PCRUCSCncRNANIAAARMAFDRmRNA3′ untranslated regions3′UTRcDNADNAdeoxyribonucleic acidcomplementary deoxyribonucleic acidRNAribonucleic acidAlcoholismstandard deviationmiRNA expressionUniversity of California, Santa Cruzmessenger ribonucleic acidmicro ribonucleic acidRINPMIPost mortem intervalHuman frontal cortexscaRNAGC contentNational Institute of Child Health and Human DevelopmentNational Institute on Alcohol Abuse and Alcoholismfalse discovery rateMiRNApolymerase chain reactionreverse transcription polymerase chain reactionPCR
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Authors
A.M. Manzardo, S. Gunewardena, M.G. Butler,