Bioinfomatics analysis for unraveling the mechanisms of EIF3D-mediated binding and regulation in the non-modified regions of target RNA in liver cancer
LIU Ziyao
LIU Siyuan
CHEN Yiqiang
DAI Zhiyan
LI Jingjing
SHEN Jie
XIE Zhengyao
Abstract：Objective To investigate the target binding pattern and transcriptional level regulation mechanism of the eukaryotic translation initiation factor 3 subunit D(EIF3D)gene in liver cancer by using bioinformatics methods and public databases.Methods The expression and survival differences of EIF3D in liver cancer were obtained from tumor public databases.The enhanced UV cross-linking innmunoprecipitation(eCLIP)data of EIF3D in the liver cancer HepG2 cell lines was analyzed using public databases to identify target binding sites,followed by annotation of target binding regions and gene sets using HOMER and statistical screening.Gene ontology(GO)/Kyoto encyclopedia of genes and genomes(KEGG)and PPI analysis were conducted based on this gene set.Differential analysis was carried out on EIF3D knockdown RNA-seq data to identify a set of differentially expressed genes,along with GO/KEGG and PPI analysis,and downstream personalized database analysis on this gene set.Results Data from public databases indicated a significant increase in EIF3D expression levels in liver cancer tissues(P＜0.001),with markedly lower survival rates in individuals with high EIF3D expression compared to those with low expression(P＜0.001).EIF3D was not expressed in bile duct cells of normal liver tissues,but weakly expressed in liver cells;EIF3D was moderately expressed in the cytoplasm and membrane of liver cancer cells.In the liver cancer HepG2 cell lines,EIF3D showed a tendency to bind to the exon region of target genes,influencing processes such as cell differentiation,cell cycle progression,and mRNA metabolism through target RNA regulation.The down-regulated target gene set post EIF3D knockdown was associated with processes like mitosis,cell cycle,and DNA repair,with an interaction network presented in this gene set:ATAD2-TOP2A-TPX2-KNTC1-FANCA,which was significantly up-regulated in liver cancer and had an adverse impact on prognosis.Conclusion EIF3D may regulate transcriptional levels by binding to the RNA non-modified regions of target gene networks,thereby facilitating the progression of liver cancer.
Keywords：Liver cancerEukaryotic translation initiation factor 3 subunit DBioinformaticsRNA binding protein
Publication Date：2024-08-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 779-785 )