Further analysis showed that the predicted targets of 27 up-regulated miRNAs were over-represented in the group of down-regulated mRNAs (hypergeometric p< 0.05, FDR < 5%, Table 2). This was also corroborated by the analysis on the randomized control group (z-test P = 0.00099), where only 14 out of 35 randomly selected miRNAs display the equivalent behaviour. Remarkably, this core group of 27 miRNAs is predicted to regulate 128 out of the 131 (98%) down-regulated mRNAs that are putative miRNA-targets. This underscores the central role played by these 27 miRNAs in regulating gene expression in the frontal cortex in response to chronic alcohol consumption.