Comprehensive analysis of biological networks and the eukaryotic initiation factor 4A‐3 gene as pivotal in hepatocellular carcinoma. Issue 10 (3rd January 2020)

• Record Type: Journal Article
• Authors: Lin, Yan; Liang, Rong; Mao, Yingwei; Ye, Jiazhou; Mai, Rongyun; Gao, Xing; Liu, Ziyu; Wainwright, Taylor; Li, Qian; Luo, Min; Ge, Lianying; Li, Yongqiang; Zou, Donghua
• Is Part Of: Journal of cellular biochemistry. Volume 121:Issue 10(2020)
• Page Start: 4094
• Page End: 4107
• Publication Date: 2020-01-03
• Subjects: biological network -- cell cycle -- EIF4A3 -- hepatocellular carcinoma -- kinase -- transcription factor; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.29596
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Eukaryotic initiation factor 4A‐3 (EIF4A3) is a core component of the exon junction complex (EJC). 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‐time 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‐protein 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‐occurring 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‐associated transcription factors. Finally, crosslinking‐immunoprecipitation and high‐throughput sequencing (CLIP‐seq) data showed that EIF4A3 protein binds to multiple exon regions of the cell cycle regulatory genes cyclin‐dependent 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‐depth study of EIF4A3 in carcinogenesis. Abstract : Eukaryotic initiation factor 4A‐3 (EIF4A3) is a vital splicing factor and a core component of the exon junction complex. Normally, this factor modulates the expression of various apoptotic and cell cycle‐related genes. Previous work has focused on EIF4A3 dysfunction were associated with carcinogenesis. However, no system analysis on its role specifically in hepatocellular carcinoma (HCC). Based on The Cancer Genome Atlas database combined with histological analysis, we are very excited to share our story on the role of EIF4A3 in HCC from the expression, prognostic value, genomic alteration, and various function networks. The study will shed light on the potential biological role of EIF4A3 in HCC.