Eukaryotic Translation Initiation Factor 3b is both a Promising Prognostic Biomarker and a Potential Therapeutic Target for Patients with Clear Cell Renal Cell Carcinoma

Zang, Yuanwei; Zhang, Xiang; Yan, Lei; Gu, Gang-Li; Li, Dawei; Zhang, Yongzhen; Fang, Liang; Fu, Shanlin; Ren, Juchao; Xu, Zhonghua

doi:10.7150/jca.19594

Cited by 31 publications

(40 citation statements)

References 52 publications

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“…EIF3 promotes mRNA binding to 40S subunits and prevents premature binding of large ribosomal subunits to regulate eukaryotic protein synthesis [3] . Emerging studies have demonstrated that eIF3 plays a role in tumorgenesis and tumor progression [11] . Zang et al reported that eIF3b was a potential prognostic indicator and therapeutic target for ccRCC [11] , that EIF3b knockdown inhibited the Akt signaling pathway, thus suppressing cell proliferation by triggering apoptosis.…”

Section: Introductionmentioning

confidence: 99%

“…Emerging studies have demonstrated that eIF3 plays a role in tumorgenesis and tumor progression [11] . Zang et al reported that eIF3b was a potential prognostic indicator and therapeutic target for ccRCC [11] , that EIF3b knockdown inhibited the Akt signaling pathway, thus suppressing cell proliferation by triggering apoptosis. In addition, EIF3b inhibition also impaired epithelial-tomesenchymal transition (EMT), thus suppressing migration and invasion in vitro and in vivo [11] .…”

Section: Introductionmentioning

confidence: 99%

“…Zang et al reported that eIF3b was a potential prognostic indicator and therapeutic target for ccRCC [11] , that EIF3b knockdown inhibited the Akt signaling pathway, thus suppressing cell proliferation by triggering apoptosis. In addition, EIF3b inhibition also impaired epithelial-tomesenchymal transition (EMT), thus suppressing migration and invasion in vitro and in vivo [11] . It was found in our previous study that the expression level of EIF3D in the RCC tissue was higher than that in the paired adjacent normal tissues, and that the expression level of EIF3D was positively correlated with TNM stage and tumor size [3] .…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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“…Also, high levels of eIF3b have been detected in several tumors, such as hepatocellular carcinoma (HCC) 46 , osteosarcoma 47 , clear cell renal cell carcinoma (ccRCC) 48 , bladder cancer 49 , prostate cancer 49 , esophageal squamous cell carcinoma (ESCC) 50 , glioblastoma 51 , colon cancer 52 , breast cancer 53 and gastric cancer 54 . In ccRCC, high expression of eIF3b is not only associated with an aggressive tumor phenotype, but also is an independent predictor of patient prognosis 48 . Overexpression of eIF3b in ESCC was found to be associated with lymph node metastasis, tumor depth, and advanced TNM stage, and ESCC patients with a high- level of eIF3b expression have a shorter overall survival and disease-free survival than those with lower eIF3b expression (Fig.…”

Section: Functions Of Eif3bmentioning

confidence: 99%

The Biological Roles of Translation Initiation Factor 3b

Feng

2018

Int. J. Biol. Sci.

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Translation has important roles in almost all physiological and pathological processes, and translation initiation factors are particularly relevant to the translation initiation step, which is the most important step in translation regulation. Translation initiation factor 3b (eIF3b), a key subunit of the largest translation initiation factor 3 (eIF3), is widely considered a scaffold protein that acts to ensure the accuracy of translation initiation. A series of recent finds has revealed that eIF3 is closely related to oncogenesis. However, the concrete mechanism by which eIF3b is involve in carcinogenesis remains elusive. Here, we summarize a series of research findings regarding the relationship between eIF3b, translation and cancer.

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“…3 (VI)] comes from a study of the effects of knockdown of the gene family of eukaryotic translation initiation factors (EIF) by RNAi in MCF10A cells. EIF3b is a promising prognostic biomarker and a potential therapeutic target for patients with clear cell renal cell carcinoma[32], and EIF4GI is a target for cancer therapeutics[33].The top pathway inTable S2[Fig. 4 (I)] is the 'Pathway of regulation of IGF activity by IGFBP'.…”

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confidence: 99%

Identification of miRNA signatures for kidney renal clear cell carcinoma using the tensor-decomposition method

Taguchi

2019

Preprint

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AbstractCancer is a highly complex disease caused by multiple genetic factors. MicroRNA (miRNA) and mRNA expression profiles are useful for identifying prognostic biomarkers for cancer. Kidney renal clear cell carcinoma (KIRC), which accounts for more than 70% of all renal malignant tumour cases, was selected for our analysis.Traditional methods of identifying cancer prognostic markers may not be accurate. Tensor decomposition (TD) is a useful method uncovering the underlying low-dimensional structures in the tensor. The TD-based unsupervised feature extraction method was applied to analyse mRNA and miRNA expression profiles. Biological annotations of the prognostic miRNAs and mRNAs were examined utilizing the pathway and oncogenic signature databases DIANA-miRPath and MSigDB.TD identified the miRNA signatures and the associated genes. These genes were found to be involved in cancer-related pathways, and 23 genes were significantly correlated with the survival of KIRC patients. We demonstrated that the results are robust and not highly dependent upon the databases we selected. Compared with traditional supervised methods tested, TD achieves much better performance in selecting prognostic miRNAs and mRNAs.These results suggest that integrated analysis using the TD-based unsupervised feature extraction technique is an effective strategy for identifying prognostic signatures in cancer studies.

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Eukaryotic Translation Initiation Factor 3b is both a Promising Prognostic Biomarker and a Potential Therapeutic Target for Patients with Clear Cell Renal Cell Carcinoma

Cited by 31 publications

References 52 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

The Biological Roles of Translation Initiation Factor 3b

Identification of miRNA signatures for kidney renal clear cell carcinoma using the tensor-decomposition method

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