Here, we report the first network analysis of AUD-associated brain miRNAs and mRNAs. Specifically, we examined AUD-associated miRNA and mRNA transcriptomic changes in multiple brain regions of AUD subjects. We also performed miRNA–mRNA pairing analysis and constructed AUD-associated and brain region-specific miRNA–mRNA regulatory networks. To understand whether miRNA and mRNA expression changes in postmortem brains of AUD subject are due to alcohol consumption, we differentiated human embryonic stem cells (hESCs) into cortical interneurons and then used hESC-derived cortical interneurons as in vitro cellular models to examine ethanol-induced miRNA and mRNA transcriptomic changes. The convergence of multiple brain region transcriptome analysis and neuronal modeling could facilitate our understanding of the neuroadaptive mechanisms of AUD.
