Using miRNA target prediction programs in combination with previous mRNA profiling, more than half of the annotated differentially expressed mRNAs (55%) were identified as potential targets. Putative targets of miRNAs were significantly over-represented among downregulated genes in alcoholics. This may indicate an inverse relationship among the over-expressed miRNAs and respective down-regulated target genes. Several studies have recently reported similar negatively correlated expression patterns relationships (Farh et al., 2005; Manakov et al., 2009; Nielsen et al., 2009; Sood et al., 2006), which may indicate a characteristic behavior of miRNA-mRNA regulatory networks. However, miRNAs may additionally function indirectlyover specific targets, e.g. through complex feed-forward and feedback loops (Hobert, 2008; Sales et al., 2010), or different combinations of miRNAs may coordinately regulate specific target genes by unknown mechanism to promote positively correlated mRNA expression patterns.
