MicroRNA miR-203 is the upregulated miRNA in human alcoholics with the highest over-representation of targets among inversely correlated differentially expressed mRNA transcripts from the same samples (Lewohl et al., 2011). This miRNA has been suggested to regulate IL6 and IFNγ signaling through targeting of the Suppressor of Cytokine Signaling 3 (SOCS3; Sonkoly et al., 2007). SOCS3 is part of a negative feedback loop in cytokine signaling that inhibits the activation of transcription factor STAT3, part of the JAK–STAT signaling cascade that is the basis of the signal transduction mechanism for many cytokine receptors. Upregulation of miR-203 may hence lead to increased and/or longer inflammatory response. Furthermore, miR-203 is predicted to target above mentioned CXCR4 (component of the LPS-sensing complex), which is the alcohol-downregulated mRNA most significantly over-targeted by miRNAs in human alcoholics (Lewohl et al., 2011). These appear to represent compensatory effects that, on one hand, aim at downregulating responsiveness to the LPS insult while, on the other, aim at maintaining required levels of neuroimmune activity. These results support the notion that CXCR4 and miRNAs regulating its expression are important players modulating alcohol actions in the brain of human alcoholics.
