Up-regulation of microRNAs in brain of human alcoholics.
- Authors
- Lewohl, Joanne M; Nunez, Yury O; Dodd, Peter R; Tiwari, Gayatri R; Harris, R Adron; Mayfield, R Dayne
- Year
- 2011
- Journal
- Alcoholism, clinical and experimental research
- PMID
- 21651580
- DOI
- 10.1111/j.1530-0277.2011.01544.x
- PMCID
- PMC3170679
BACKGROUND: MicroRNAs (miRNAs) are small, noncoding oligonucleotides with an important role in posttranscriptional regulation of gene expression at the level of translation and mRNA degradation. Recent studies have revealed that miRNAs play important roles in a variety of biological processes, such as cell proliferation, neuronal differentiation, developmental timing, synapse function, and neurogenesis. A single miRNA can target hundreds of mRNA transcripts for either translation repression or degradation, but the function of many human miRNAs is not known. METHODS: miRNA array analysis was performed on the prefrontal cortex of 27 individual human cases (14 alcoholics and 13 matched controls). Target genes for differentially expressed miRNAs were predicted using multiple target prediction algorithms and a consensus approach, and predicted targets were matched against differentially expressed mRNAs from the same samples. Over- and under-representation analysis was performed using hypergeometric probability and z-score tests. RESULTS: Approximately 35 miRNAs were significantly up-regulated in the alcoholic group compared with controls. Target prediction showed a large degree of overlap with our published cDNA microarray data. Functional classification of the predicted target genes of the regulated miRNAs includes apoptosis, cell cycle, cell adhesion, nervous system development, and cell-cell signaling. CONCLUSIONS: These data suggest that the reduced expression of genes in human alcoholic cases may be because of the up-regulated miRNAs. Cellular processes fundamental to neuronal plasticity appear to represent major targets of the suggested miRNA regulation.
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| Name | Type |
|---|---|
| 7900HT Fast Real-Time PCR System local | drug |
| ABI2 local | gene |
| Acute effects of alcohol local | phenotype |
| Agilent 2100 Bioanalyzer | drug |
| ALCAM local | gene |
| alcohol | phenotype |
| alcohol abuse | phenotype |
| alcohol dependence | phenotype |
| Alcoholic cases local | cohort |
| alcoholism | phenotype |
| alcohol-related cellular mechanisms local | phenotype |
| alcohol tolerance | phenotype |
| Alzheimer's disease | phenotype |
| Alzheimerโs disease | phenotype |
| ambi_miR_12897 local | gene |
| ambi_miR_13196 local | gene |
| ambi_miR_7058 local | gene |
| ambi_miR_8488 local | gene |
| ambi_miR_8518 local | gene |
| ambi_miR_9125 local | gene |
| ambi_miR_9451 local | gene |
| Ambion | drug |
| Animal models of alcoholism local | cohort |
| ANP32E local | gene |
| Applied Biosystems | drug |
| Australian Brain Bank Network local | cohort |
| Australian Brain Donor Programs NSW Tissue Resource Centre local | cohort |
| Axon GenePix 6.0 local | drug |
| BIRC6 local | gene |
| BK channel | gene |
| brain | anatomy |
| C11ORF9 local | gene |
| cancer | phenotype |
| CANX local | gene |
| CAPN3 local | gene |
| CCDC88A | gene |
| CDC42 local | gene |
| CDKN1B local | gene |
| chronic alcoholism | phenotype |
| CNP local | gene |
| cocaine | phenotype |
| cognitive decline | phenotype |
| Complicated alcohol-related disorders local | phenotype |
| control | cohort |
| control group | cohort |
| controls | cohort |
| core of 17 downregulated mRNAs local | gene |
| Cultured cells local | cohort |
| dementia | phenotype |
| Dendritic complexity | phenotype |
| Dendritic density local | phenotype |
| DICER1 | gene |
| DIDO1 local | gene |
| downregulated mRNA (group of 131) local | gene |
| down-regulated mRNAs local | gene |
| DST local | gene |
| EDIL3 local | gene |
| ELOVL4 local | gene |
| Elovl5 | gene |
| ELOVL7 local | gene |
| ethanol consumption | phenotype |
| experimental dataset local | cohort |
| FAR1 local | gene |
| FBXL3 local | gene |
| FERMT2 local | gene |
| frontal cortex | anatomy |
| GenExsoftware local | drug |
| heavy drinking | phenotype |
| hepatic encephalopathy | phenotype |
| hsa-let-7g local | drug |
| hsa-let-7g local | gene |
| hsa-miR-152 local | drug |
| hsa-miR-152 local | gene |
| hsa-miR-15b local | drug |
| hsa-miR-15b local | gene |
| hsa-miR-301a local | drug |
| hsa-miR-301a local | gene |
| hsa-miR-369-3p local | drug |
| hsa-miR-369-3p local | gene |
| hsa-miR-423-5p local | gene |
| hsa-miR-7 local | drug |
| hsa-miR-7 local | gene |
| human alcoholics | phenotype |
| LAMP2 local | gene |
| LASS2 local | gene |
| let-7 local | drug |
| let-7g local | gene |
| Liu et al., 2006 local | cohort |
| Liver cirrhosis | phenotype |
| LMO7 local | gene |
| microRNA (miRNA) local | drug |
| miR-144 local | drug |
| miR-144 local | gene |
| miR-146a local | drug |
| miR-152 local | gene |
| miR-15b local | gene |
| miR-18a local | drug |
| miR-18a local | gene |
| miR-194 local | drug |
| miR-203 local | drug |
| miR-203 local | gene |
| miR-301a local | gene |
| miR-339-5p local | drug |
| miR-339-5p local | gene |
| miR-34c-5p local | drug |
| miR-34c-5p local | gene |
| miR-380 local | drug |
| miR-380 local | gene |
| miR-519b-3p local | drug |
| miR-580 local | drug |
| miR-580 local | gene |
| miR-586 local | drug |
| miR-586 local | gene |
| miR-665 local | drug |
| miR-7 local | drug |
| miR-7 local | gene |
| miR-802 local | drug |
| miR-802 local | gene |
| miR-9 | drug |
| mirBase 9.0 local | drug |
| miRNA | drug |
| miRNA-AI microarray local | drug |
| miRNA expression changes local | phenotype |
| miRNA Recognition Elements (MREs) local | drug |
| miRNAs | drug |
| miRNA samples local | drug |
| mirVana miRNA Isolation Kit local | drug |
| mirVana miRNA Labeling Kit local | drug |
| morphine | drug |
| mRNA | drug |
| multiple miRNAs local | gene |
| Neonatal rats | cohort |
| neuroadaptation | phenotype |
| neurodegenerative disease | phenotype |
| nicotine | drug |
| NIH-Duke University microarray facility local | cohort |
| OSBPL11 local | gene |
| over-targeted mRNA group local | gene |
| Pelizaeus-Merzbacher disease | phenotype |
| PIK3C2B local | gene |
| PLCL1 | gene |
| PLP1 | gene |
| prefrontal cortex | anatomy |
| Queensland Brain Bank local | cohort |
| randomized control group local | cohort |
| RDX local | gene |
| RIPK2 local | gene |
| RNU44 local | gene |
| RNU6B local | gene |
| RYBP local | gene |
| SCARB2 local | gene |
| SCD | gene |
| SGBC local | gene |
| SGK1 local | gene |
| SGMS1 local | gene |
| SMARCA5 | gene |
| SNORD44 local | gene |
| SPAST local | gene |
| Spastic paraplegia 2 local | phenotype |
| SPG20 local | gene |
| SPOCK1 local | gene |
| SPTLC2 local | gene |
| study cohort | cohort |
| TaqManยฎ MicroRNA Assays local | drug |
| TaqManยฎ MicroRNA Reverse Transcription Kit local | drug |
| TEX2 local | gene |
| TGFB2 | gene |
| TIMP2 local | gene |
| TKT local | gene |
| TNKS | gene |
| TP53INP1 local | gene |
| U6BsnRNA local | gene |
| UFSP2 local | gene |
| ULK2 local | gene |
| up-regulated miRNAs local | drug |
| up-regulated miRNAs local | gene |
| upregulated miRNAs (group of 35) local | drug |
| USP31 local | gene |
| Wernicke Korsakoff syndrome local | phenotype |
| Wernicke-Korsakoff syndrome | phenotype |
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