Our group recently published the first comprehensive study describing the impact of alcohol on microRNA levels in the brain of human alcoholics (Lewohl et al., 2011). For this, we conducted miRNA and mRNA microarray studies in prefrontal cortex (PFC) of postmortem human brain samples and developed an integrative statistical analysis highlighting differentially expressed miRNAs that inversely correlated with respective differentially expressed mRNA targets. The report uncovered a majoritarian effect of alcohol on activation of miRNA expression levels and highlighted about 35 human miRNAs that were upregulated in the alcoholic brain samples (Table 1). Interestingly, mRNAs that were predicted to be targeted by this group of upregulated miRNAs were significantly over-represented among the alcohol-downregulated mRNAs, while no such over-representation was detected among the set of alcohol-upregulated mRNAs. This result supports a role for miRNA-dependent inhibition of gene expression in the PFC of human alcoholics. Furthermore, we found that the alcohol-upregulated miRNAs were apparently regulating their putative target genes in a combinatorial fashion (multiple miRNAs targeting the same mRNA). Such a paradigm could be exploited by the cells to either ensure inhibition of the putative targets at any cost (redundancy) or to achieve fine-tuned regulation of specific mRNA expression levels (fine-tuning).
