Comprehensive analysis of biological networks and the eukaryotic initiation factor 4A-3 gene as pivotal in hepatocellular carcinoma

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.

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Work Title Comprehensive analysis of biological networks and the eukaryotic initiation factor 4A-3 gene as pivotal in hepatocellular carcinoma
Access
Open Access
Creators
  1. Yan Lin
  2. Rong Liang
  3. Yingwei Mao
  4. Jiazhou Ye
  5. Rongyun Mai
  6. Xing Gao
  7. Ziyu Liu
  8. Taylor Wainwright
  9. Qian Li
  10. Min Luo
  11. Lianying Ge
  12. Yongqiang Li
  13. Donghua Zou
Keyword
  1. Biological network
  2. Cell cycle
  3. EIF4A3
  4. Hepatocellular carcinoma
  5. Kinase
  6. Transcription factor
License In Copyright (Rights Reserved)
Work Type Article
Publisher
  1. Journal of Cellular Biochemistry
Publication Date January 3, 2020
Publisher Identifier (DOI)
  1. https://doi.org/10.1002/jcb.29596
Deposited March 06, 2023

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Work History

Version 1
published

  • Created
  • Added 16650941-EiF4A3.pdf
  • Added Creator Yan Lin
  • Added Creator Rong Liang
  • Added Creator Yingwei Mao
  • Added Creator Jiazhou Ye
  • Added Creator Rongyun Mai
  • Added Creator Xing Gao
  • Added Creator Ziyu Liu
  • Added Creator Taylor Wainwright
  • Added Creator Qian Li
  • Added Creator Min Luo
  • Added Creator Lianying Ge
  • Added Creator Yongqiang Li
  • Added Creator Donghua Zou
  • Published
  • Updated Keyword, Publisher, Publication Date Show Changes
    Keyword
    • Biological network, Cell cycle, EIF4A3, Hepatocellular carcinoma, Kinase, Transcription factor
    Publisher
    • Journal of supramolecular structure and cellular biochemistry
    • Journal of Cellular Biochemistry
    Publication Date
    • 2020-10-01
    • 2020-01-03
  • Updated