miRNA expression profiling was performed in the frontal cortex of alcoholics [87]. A total of 35 miRNAs were up-regulated in alcoholics and used for target prediction. Interestingly, predicted miRNA targets were significantly over-represented in the set of 217 genes previously identified as down-regulated in the same postmortem samples, and most putative targets were regulated by multiple miRNAs [61]. Conversely, there were 27 miRNAs whose predicted targets were over-represented among down-regulated transcripts. Many of the down-regulated transcripts were related to lipid biosynthesis and metabolism, cytoskeleton and cell cycle control. Interestingly, the down-regulated transcript targeted by the highest number of up-regulated miRNAs encodes Dicer, a key enzyme in the generation of mature miRNAs. The authors proposed that such a negative feedback loop could serve as a mechanism for tight regulation of global miRNA levels and maintenance of cellular homeostasis.
