The function and clinical significance of eIF3 in cancer

Yin, Yuting; Long, Jiali; Sun, Yanqin; Li, Hongmei; Jiang, Enping; Zeng, Chao; Zhu, Wei

doi:10.1016/j.gene.2018.06.034

Cited by 52 publications

(39 citation statements)

References 47 publications

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“…Eukaryotic translation initiation factor 3 (EIF3) is one of the largest and most complex eukaryotic translation initiation factors containing 13 subunits (eIF3a-eIF3m), which plays an important role in the regulation of eukaryotic translation [10] . EIF3 promotes mRNA binding to 40S subunits and prevents premature binding of large ribosomal subunits to regulate eukaryotic protein synthesis [3] .…”

Section: Introductionmentioning

confidence: 99%

EIF3D promotes sunitinib resistance of renal cell carcinoma by interacting with GRP78 and inhibiting its degradation

et al. 2019

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Background: Sunitinib is one of the multi-targeted tyrosine kinase inhibitors for the treatment of renal cell carcinoma (RCC) at present. However, its clinical efficacy is limited by chemoresistance of RCC. Our previous study found that eukaryotic translation initiation factor 3 subunit D (EIF3D) was an oncogene in the development and progression of RCC but little is known about whether EIF3D participated in sunitinib resistance of RCC. Methods: The expression of EIF3D in the tumor tissue specimen was detected by immunohistochemistry. The effect of EIF3D on sunitinib-resistance of RCC cells was evaluated by colony formation, IC50 proliferation and in vivo tumor growth assays. The interaction between EIF3D and glucose regulated protein 78 (GRP78) was assessed by Co-IP and Western blot assays. Finding: EIF3D expression was found higher in 786-OR and ACHN-R cells with acquired sunitinib resistance than that in 786-O and ACHN cells sunitinib to sensitive. The EIF3D level was also up-regulated in sunitinib-chemoresistant tumor tissues compared with chemosensitive tumor tissues. Functional study showed that EIF3D knockdown decreased cell viability with sunitinib treatment. Mechanistical study demonstrated that EIF3D interacted with GRP78 and enhanced protein stability through blocking the ubiquitin-mediated-proteasome degradation of GRP78. GRP78 overexpression induced sunitinib resistance of RCC cells by triggering the unfolded protein response, whereas GRP78 silencing inhibited cell viability. Forced expression of GRP78 eliminated the inhibitory effect of EIF3D silencing on cell growth in vitro and in vivo. Interpretation: our results indicate that EIF3D played an important role in sunitinib resistance of RCC cells, suggesting that it may prove to be a potential therapeutic target for RCC.

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Section: Introductionmentioning

confidence: 99%

EIF3D promotes sunitinib resistance of renal cell carcinoma by interacting with GRP78 and inhibiting its degradation

et al. 2019

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“…and exerts transcriptional activation/repression through forming different forms of stem loop binding with the mRNAs (64,65). Dysregulation of translation initiation and the role of EIF3 has been studied in cancers (66,67,68). Moreover, involvement of EIF3 complex in regulation of mTOR pathway, which is associated with many cancers (69,70), makes it an interesting protein to study for its regulatory role in PCa.…”

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confidence: 99%

Identification of key regulators in Prostate cancer from gene expression datasets of patients

Mangangcha

Malik

Küçük

et al. 2019

Preprint

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Identification of key regulators and regulatory pathways is an important step in the discovery of genes involved in cancer. Here, we propose a method to identify key regulators in prostate cancer (PCa) from a network constructed from gene expression datasets of PCa patients.Overexpressed genes were identified using BioXpress, having a mutational status according to COSMIC, followed by the construction of PCa Interactome network using the curated genes.The topological parameters of the network exhibited power law nature indicating hierarchical scale-free properties and five levels of organization. Highest degree hubs (k≥65) were selected from the PCa network, traced, and 19 of them were identified as novel key regulators, as they participated at all network levels serving as backbone. Of the 19 hubs, some have been reported in literature to be associated with PCa and other cancers. Based on participation coefficient values most of these are connector or kinless hubs suggesting significant roles in modular linkage. The observation of non-monotonicity in the rich club formation suggested the importance of intermediate hubs in network integration, and they may play crucial roles in network stabilization. The network was self-organized as evident from fractal nature in topological parameters of it and lacked a central control mechanism.

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“…In the process of eukaryotic cell translation initiation, EIF3 can bind directly to small 40S ribosome subunits, thus promoting the formation of the eukaryotic initiation factor 2-triphosphate-amino acid-tRNA (Met-tRNA) ternary complex of the 43S subunit precursor complex, and regulating the synthesis of protein in the process of protein translation 21 . Recent studies showed that EIF3 plays an important role in the occurrence and development of malignant tumors 22,23 . For example, EIF3A, the largest subunit of EIF3 family, is highly expressed in various malignant tumor tissues and has been used as a potential target for anti-cancer drugs 24 .…”

Section: Discussionmentioning

confidence: 99%

ZNF280A Promotes Lung Adenocarcinoma Development through Regulating the Expression of EIF3C

Liu

Qin

et al. 2020

Preprint

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Background: Lung cancer is the most commonly diagnosed malignant tumor worldwide. Lung adenocarcinoma (LUAD) is the most common histological subtype in non-small cell lung cancer (NSCLC). The relationship between ZNF280A and LUAD has not been demonstrated and remains unclear. Methods: In this study, it was demonstrated that ZNF280A was upregulated in LUAD tissues compared with the normal tissues. Further investigations indicated that the overexpression/knockdown of ZNF280A could promote/inhibit proliferation, colony formation and migration of LUAD cells, while inhibiting/promoting cell apoptosis. Moreover, knockdown of ZNF280A could also suppress tumorigenicity of LUAD cells in vivo. RNA-sequencing followed by Ingenuity pathway analysis (IPA) was performed for exploring downstream of ZNF280A and identified EIF3C as the potential target. Results: Furthermore, our study revealed that knockdown of EIF3C could inhibit development of LUAD in vitro, and alleviate the ZNF280A overexpression induced promotion of LUAD. Conclusions: In conclusion, our study showed, as the first time, ZNF280A as a tumor promotor for LUAD, whose function was carried out probably through the regulation of EIF3C.

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The function and clinical significance of eIF3 in cancer

Cited by 52 publications

References 47 publications

EIF3D promotes sunitinib resistance of renal cell carcinoma by interacting with GRP78 and inhibiting its degradation

EIF3D promotes sunitinib resistance of renal cell carcinoma by interacting with GRP78 and inhibiting its degradation

Identification of key regulators in Prostate cancer from gene expression datasets of patients

ZNF280A Promotes Lung Adenocarcinoma Development through Regulating the Expression of EIF3C

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