ObjectiveTo explore the comorbidity mechanism of hepatocellular carcinoma and depression based on miRNA-mRNA network.Methods(1) The microarray data of miRNA related to hepatocellular carcinoma and depression were obtained from the GEO database. The differentially expressed miRNAs (DE-miRNA) of the two datasets were analyzed by using the online tool GEO2R, respectively, and then the intersection was acquired. Target genes of various DE-miRNA were predicted in the databases of TargetScan, miRDB, miRPathDB, and miRWalk for obtaining the intersection. (2) The functional enrichment analysis and pathway enrichment analysis were performed on DE-miRNA target genes by employing the DAVID database, and the risk pathways were screened. (3) The protein-protein interaction network of DE-miRNA target genes was established by the application of the STRING database and Cytoscape 3.9.1 software, and then the central genes and key genes were screened. (4) The Microsoft Excel software and Cytoscape 3.9.1 software was used to establish DE-miRNA-mRNA-risk pathways visualized network. (5) The GEPIA2 database was employed to perform expression and survival analyses of central genes in hepatocellular carcinoma.Results(1) The up-regulated DE-miRNA of hepatocellular carcinoma and depression co-expressions were miR-1290, miR-3156-5p, down-regulated DE-miRNA were miR-575, miR-6737-3p, and the four regulated 789 target genes. (2) The biological functions involved in DE-miRNA target genes were related to immunity, inflammation, angiogenesis, and neuronal signal transduction, etc. A total of 15 risk pathways were screened, including mitogen-activated protein kinase signaling pathway, phosphatidylinositol 3-kinase/protein kinase B signaling pathway, axonal guidance, oxytocin signaling pathway, and neurenergen signaling pathway, etc. (3) A total of 10 central genes were obtained, concerning BRCA1, NOTCH1, PTEN, EGFR, ATRX, ERCC4, RAD51B, EME1, RMI1, and XRCC2, respectively. Three central genes enriched in risk pathways were regarded as key genes. (4) The established network of DE-miRNA-mRNA-risk pathways contained 10 pairs of DE-miRNA-central genes combinations, and 13 combinations of DE-miRNA-key genes-risk pathways. (5) Compared with the normal group, BRCA1, PTEN, ATRX, ERCC4, RAD51B, EME1, RMI1, and XRCC2 were high-expressed in the hepatocellular carcinoma group, and NOTCH1 and EGFR were low-expressed in the hepatocellular carcinoma group (P＜0.01). BRCA1, EME1, RMI1, and XRCC2 were related to the survival rate of patients with hepatocellular carcinoma (P＜0.05). ConclusionMiR-1290, miR-3156-5p, miR-575, and miR-6737-3p may be the co-regulated factors of hepatocellular carcinoma and depression. They may thus regulate approaches to inflammatory responses, tumor immune responses, nerve conduction, etc.,and further participate the occurrence and development of hepatocellular carcinoma and depression through acting on multiple target genes. In addition, the four target genes of BRCA1, EME1, RMI1, and XRCC2 are closely related to prognosis of patients with hepatocellular carcinoma.

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