based study, where highly significant positive miRNA:mRNA correlations were detected in the PFC of mice undergoing acute alcohol exposure [22]. One potential explanation is that the positive miRNA:mRNA expression correlations observed in the animal model are the result of an uncompensated miRNA response to the increase in gene expression following the alcohol consumption. Considering that our postmortem sample consists of chronic alcoholics with drinking histories of several decades, attributing our positive miRNA:mRNA module correlations to a temporal artifact seems unlikely. A more plausible explanation, which stems directly from the negative regulatory capacity of miRNA function, could be that the observed positive correlations reflect secondary miRNA targets, as the expression of such secondary miRNA targets are expected to be positively correlated with miRNA expression [77]. Regardless of the mechanism by which these positive correlations are occurring, we are the first to report that such positive correlations appear to be preserved in chronic alcoholic subjects and that these may reflect either an adaptive or decompensated state resulting from excessive alcohol consumption.
