A recurring theme evidenced in our analysis is the extensive combinatorial targeting by which miRNA apparently exert an “over-zealous” control to fine tune the expression of specific targets. A combinatorial paradigm in miRNA function could help explain how miRNA could be achieving process-related specificity despite the fact that they are known to target a wide variety and number of distinct targets. Support for this idea has started to accumulate and its impact only recently highlighted. For example, while studying the global and local architecture of the mammalian miRNA-transcription factor (TF) regulatory network, Shalgi and collaborators found extensive interactions between miRNAs and between miRNAs and TFs, and suggested that “combinatorics may also have the advantage of allowing multiple sources of information, each represented by a single miR, to be integrated into the regulation of individual transcripts” (Shalgi et al., 2007). The potential combinatorial regulation of DICER1, the down-regulated alcohol-responsive gene with the greatest over-representation of miRNA targeting events in our dataset, could have important implications for understanding the regulatory events taking place under chronic alcohol abuse. Dicer is a key ribonuclease
