the network analysis of dysregulated and negatively correlated miRNA–mRNA pairs in six of the eight brain regions of AUD subjects (Figs. S13 and S14). Although these three top pathways were not found to be regulated by differentially expressed and negatively correlated miRNA–mRNA pairs identified in ethanol-exposed hESC-derived cortical interneurons, four other pathways [Sirtuin Signaling, Opioid Signaling, NRF2-mediated Oxidative Stress Response, and interleukin-1 (IL-1) Signaling] were uncovered (Table S15). Except the IL-1 Signaling pathway, three other pathways were also identified by the analysis of Set 1 and Set 2 samples. Similar to the IL-8 Signaling pathway, the IL-1 Signaling pathway can also regulate immune response or inflammation caused by alcohol [50]. Therefore, multiple addiction-linked pathways influenced by AUD-associated miRNA–mRNA regulatory networks could contribute to the occurrence of AUD.
