scholarly journals Eukaryotic Translation Initiation Factor 3 Subunit B Promotes Head And Neck Cancer Via CEBPB Translation

Author(s):  
Chengzhi Xu ◽  
Yupeng Shen ◽  
Yong Shi ◽  
Ming Zhang ◽  
Liang Zhou

Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type worldwide. Deregulation of mRNA translation is a frequent feature of cancer. Eukaryotic Translation Initiation Factor 3 Subunit B (EIF3B) has reported as oncogenes in cancer. However, the role of EIF3B in HNSCC remains unclear. Methods: In this study, the clinical significance of EIF3B expression in TCGA was analyzed. Then the expression of EIF3B was knockdown, and its role in HNSC was revealed. To explore the molecular mechanism of EIF3B, we applied RNA sequencing and proteomics, and deregulated pathways were acquired. RNA immunoprecipitation (RIP) sequencing was conducted to uncover the targeting mRNAs of EIF3B. Potential targets of EIF3B were validated with TCGA datasets.Results: EIF3B serves a hazardous prognostic marker in HNSCC. Besides, EIF3B promotes HNSCC proliferation and progression in vitro and in vivo. EIF3B promotes CEBPB translation and activate MAPK pathway. IL6R and CCNG2 is a target of EIF3B regulated CEBPB translation. Conclusion: In sum, this study reveals EIF3B as a novel oncogene in HNSCC, by promoting CEBPB translation and IL6R expression.

1997 ◽  
Vol 17 (12) ◽  
pp. 6876-6886 ◽  
Author(s):  
S Z Tarun ◽  
A B Sachs

mRNA translation in crude extracts from the yeast Saccharomyces cerevisiae is stimulated by the cap structure and the poly(A) tail through the binding of the cap-binding protein eukaryotic translation initiation factor 4E (eIF4E) and the poly(A) tail-binding protein Pab1p. These proteins also bind to the translation initiation factor eIF4G and thereby link the mRNA to the general translational apparatus. In contrast, uncapped, poly(A)-deficient mRNA is translated poorly in yeast extracts, in part because of the absence of eIF4E and Pab1p binding sites on the mRNA. Here, we report that uncapped-mRNA translation is also repressed in yeast extracts due to the binding of eIF4E to eIF4G. Specifically, we find that mutations which weaken the eIF4E binding site on the yeast eIF4G proteins Tif4631p and Tif4632p lead to temperature-sensitive growth in vivo and the stimulation of uncapped-mRNA translation in vitro. A mutation in eIF4E which disturbs its ability to interact with eIF4G also leads to a stimulation of uncapped-mRNA translation in vitro. Finally, overexpression of eIF4E in vivo or the addition of excess eIF4E in vitro reverses these effects of the mutations. These data support the hypothesis that the eIF4G protein can efficiently stimulate translation of exogenous uncapped mRNA in extracts but is prevented from doing so as a result of its association with eIF4E. They also suggest that some mRNAs may be translationally regulated in vivo in response to the amount of free eIF4G in the cell.


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