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Abnormalities in EIF4A3 are associated with carcinogenesis. The present study aimed to determine the biological role of EIF4A3 in hepatocellular carcinoma (HCC). Our study is based on the analysis of HCC sequencing data from public databases. We first used the Gene Expression Profiling Interactive Analysis tool and ONCOMINE to analyze the EIF4A3 expression, and the results were validated in human clinical tissues by a quantitative real\u2010time polymerase chain reaction, Western blot, and immunohistochemical. Then, we used cBioPortal to identify EIF4A3 alterations and function networks. Finally, we created a network of genes that were positively correlated with EIF4A3 using LinkedOmics, and analyzed this network using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. For the genes identified, we also analyzed the relevant kinase and transcription factor target networks as well as the protein\u2010protein interaction networks. Our results show that EIF4A3 was overexpressed in HCC tissues in comparison with normal tissues, and high EIF4A3 expression was significantly associated with poor prognosis. Analysis of the functional networks of genes that were co\u2010occurring with EIF4A3 amplification revealed connections with several chemokine signaling pathways. Furthermore, genes that positively correlated with EIF4A3 were mainly related to cell cycle and spliceosome pathways, several cell cycle regulatory kinases, and tumor\u2010associated transcription factors. Finally, crosslinking\u2010immunoprecipitation and high\u2010throughput sequencing (CLIP\u2010seq) data showed that EIF4A3 protein binds to multiple exon regions of the cell cycle regulatory genes cyclin\u2010dependent kinases 1 and 2 and transcription factor E2F1. Our study unveils potential biological networks in HCC and the pivotal role of EIF4A3 as a bridging protein, highlighting the need for an in\u2010depth study of EIF4A3 in carcinogenesis.<\/jats:p>","DOI":"10.1002\/jcb.29596","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T09:32:30Z","timestamp":1578043950000},"page":"4094-4107","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Comprehensive analysis of biological networks and the eukaryotic initiation factor 4A\u20103 gene as pivotal in hepatocellular carcinoma"],"prefix":"10.1002","volume":"121","author":[{"given":"Yan","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Medical Oncology Affiliated Tumor Hospital of Guangxi Medical University  Nanning Guangxi 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