Comprehensive analysis of biological networks and the eukaryotic initiation factor 4A-3 gene as pivotal in hepatocellular carcinoma.
CDC2 Protein Kinase
/ genetics
Carcinogenesis
Carcinoma, Hepatocellular
/ genetics
Cell Cycle
/ genetics
Cyclin-Dependent Kinase 2
/ genetics
DEAD-box RNA Helicases
/ genetics
E2F1 Transcription Factor
/ genetics
Eukaryotic Initiation Factor-4A
/ genetics
Exons
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Humans
Liver Neoplasms
/ genetics
Prognosis
Protein Interaction Maps
RNA, Messenger
/ genetics
Transcriptome
EIF4A3
biological network
cell cycle
hepatocellular carcinoma
kinase
transcription factor
Journal
Journal of cellular biochemistry
ISSN: 1097-4644
Titre abrégé: J Cell Biochem
Pays: United States
ID NLM: 8205768
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
01
06
2019
accepted:
09
12
2019
pubmed:
4
1
2020
medline:
13
7
2021
entrez:
4
1
2020
Statut:
ppublish
Résumé
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.
Substances chimiques
E2F1 Transcription Factor
0
E2F1 protein, human
0
RNA, Messenger
0
CDC2 Protein Kinase
EC 2.7.11.22
CDK1 protein, human
EC 2.7.11.22
CDK2 protein, human
EC 2.7.11.22
Cyclin-Dependent Kinase 2
EC 2.7.11.22
Eukaryotic Initiation Factor-4A
EC 2.7.7.-
EIF4A3 protein, human
EC 3.6.1.-
DEAD-box RNA Helicases
EC 3.6.4.13
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4094-4107Informations de copyright
© 2020 Wiley Periodicals, Inc.
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