title: Over-expression of the miRNA cluster at chromosome 14q32 in the alcoholic brain correlates with suppression of predicted target mRNA required for oligodendrocyte proliferation.
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≥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.affiliation: Department of Psychiatry and Behavioral Sciences, University of Kansas School of Medicine, Kansas City, KS 66160, USA. amanzardo@kumc.edu
authors.forename: A M
authors.initials: AM
authors.lastname: Manzardo
authors.forename: S
authors.initials: S
authors.lastname: Gunewardena
authors.forename: M G
authors.initials: MG
authors.lastname: Butler
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000235:genetics*; D001921:Brain / Q000378:metabolism*; D049109:Cell Proliferation; D002883:Chromosomes, Human, Pair 14; D016000:Cluster Analysis; D005091:Exons; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D005810:Multigene Family; D009836:Oligodendroglia / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
keywords: 14q32 chromosome region; 3′ untranslated regions; 3′UTR; Alcoholism; DNA; Exon expression; FDR; GC content; Human frontal cortex; NIAAA; NICHD; National Institute of Child Health and Human Development; National Institute on Alcohol Abuse and Alcoholism; Oligodendrocyte proliferation; PCR; PMI; RIN; RMA; RNA; RT-PCR; SD; UCSC; UPGMA; University of California, Santa Cruz; cDNA; complementary deoxyribonucleic acid; deoxyribonucleic acid; false discovery rate; guanine-cytosine content; mRNA; messenger ribonucleic acid; miRNA; miRNA expression; micro ribonucleic acid; ncRNA; non-coding ribonucleic acid; polymerase chain reaction; post mortem interval; reverse transcription polymerase chain reaction; ribonucleic acid; ribonucleic acid integrity number; robust multichip average; scaRNA; small Cajal body-specific ribonucleic acid; small nucleolar ribonucleic acid; snoRNA; standard deviation; un-weighted average distance