Global expression profiling identified 531 differentially expressed mRNAs in the frontal cortex of alcoholics. Annotations are currently available for 342; 217 were down-regulated and 125 were up-regulated (Liu et al., 2006). In general, the expression levels of miRNAs and their mRNA targets are inversely correlated (Guo et al., 2010), with up-regulation of miRNAs correlated with down-regulation of their respective targets. Because all of the differentially expressed miRNAs in our dataset were up-regulated, we first considered only those mRNAs which were down-regulated in our microarray study and conducted over-representation analysis of predicted miRNA target sites in our set of down-regulated mRNAs. Predicted miRNA targets were significantly over-represented in our set of down-regulated mRNAs (experimental proportion 131/217 vs. mean randomized trial proportion 95/217, z-test P = 0.00059). There was no such over-representation amongst the set of up-regulated mRNAs. This finding supports a role for miRNA-regulation of these genes that is consistent with the current understanding that miRNA expression levels are generally inversely correlated with the expression levels of their respective mRNA targets (Guo et al., 2010).
