miRNAs were significantly up-regulated in the frontal cortex of human alcoholics (Lewohl et al., 2011; Manzardo et al., 2014; Nunez and Mayfield, 2012), and may have roles in apoptosis, cell cycle regulation, cell adhesion, oligodendrocyte proliferation, synaptic transmission, ion channel function, and immune signaling based on functional classification of predicted target genes (Nunez and Mayfield, 2012). Predicted target mRNAs of up-regulated miRNAs were significantly over-represented among alcohol-induced down-regulated mRNAs (Lewohl et al., 2011; Nunez and Mayfield, 2012), suggesting a role for miRNA-dependent inhibition of gene expression in human alcoholics. Many of the up-regulated miRNAs (miR-15, miR-34, miR-92, miR-140, miR-146, miR-152, miR-194, miR-196, miR-203, miR-369, and let-7) target known modulators of immune signaling, including innate immune toll-like receptors (TLRs) (Nunez and Mayfield, 2012). The miR-146 family was previously shown to be up-regulated by bacterial endotoxin lipopolysaccharides (LPS), which mediate TLR signaling through negative feedback loops involving down-regulation of IL-1 receptor-associated kinase 1 (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6) protein levels (Taganov et al., 2006). TLR signaling has been linked to alcohol consumption in human alcoholics and rodent models
