Elevated expression of eukaryotic translation initiation factor 3H is associated with proliferation, invasion and tumorigenicity in human hepatocellular carcinoma

Zhu, Qing; Zeng, Xiao-Chuan; Li, Yun; Yan, Jianjun; Duan, Rui; Du, Zhifeng

doi:10.18632/oncotarget.10222

Cited by 35 publications

(34 citation statements)

References 26 publications

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“…At the protein level, eIF3e affects proliferation and survival of glioblastoma cells (Sesen et al, 2014), is involved in colon tumor progression (Li et al, 2014) and breast tumor formation, (Suo et al, 2015) progression (Grzmil et al, 2010) and metastasis (Gillis and Lewis, 2013). High levels of eIF3h maintain the malignancy of several cancer cell lines in vitro (Zhang et al, 2008) and have been indeed observed in breast, prostate and hepatocellular carcinomas (Hershey, 2015; Zhu et al, 2016). How the targeting of these initiation factors help to explain superior activity of CM16 against cancerous over non-cancerous cells remains to be investigated.…”

Section: Discussionmentioning

confidence: 94%

A harmine-derived beta-carboline displays anti-cancer effects in vitro by targeting protein synthesis

Carvalho

Chu

Meinguet

et al. 2017

European Journal of Pharmacology

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Growing evidence indicates that protein synthesis is deregulated in cancer onset and progression and targeting this process might be a selective way to combat cancers. While harmine is known to inhibit DYRK1A and intercalate into the DNA, tri-substitution was shown previously to modify its activity profile in favor of protein synthesis inhibition. In this study, we thus evaluated the optimized derivative CM16 in vitro anti-cancer effects unfolding its protein synthesis inhibition activity. Indeed, the growth inhibitory profile of CM16 in the NCI 60-cancer-cell-line-panel correlated with those of other compounds described as protein synthesis inhibitors. Accordingly, CM16 decreased in a time- and concentration- dependent manner the translation of neosynthesized proteins in vitro while it did not affect mRNA transcription. CM16 rapidly penetrated into the cell in the perinuclear region of the endoplasmic reticulum where it appears to target translation initiation as highlighted by ribosomal disorganization. More precisely, we found that the mRNA expression levels of the initiation factors EIF1AX, EIF3E and EIF3H differ when comparing resistant or sensitive cell models to CM16. Additionally, CM16 induced eIF2α phosphorylation. Those effects could explain, at least partly, the CM16 cytostatic anti-cancer effects observed in vitro while neither cell cycle arrest nor DNA intercalation could be demonstrated. Therefore, targeting protein synthesis initiation with CM16 could represent a new promising alternative to current cancer therapies due to the specific alterations of the translation machinery in cancer cells as recently evidenced with respect to EIF1AX and eIF3 complex, the potential targets identified in this present study.

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Section: Discussionmentioning

confidence: 94%

A harmine-derived beta-carboline displays anti-cancer effects in vitro by targeting protein synthesis

Carvalho

Chu

Meinguet

et al. 2017

European Journal of Pharmacology

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“…(30) At the chromosome 15 locus, Eif3h, encoding the eukaryotic translation initiation factor, is a candidate that is involved in the cell cycle. (31) One limitation of our study is that all F1 mice carry one chromosome from C57BL/6J and one chromosome from the HMDP. Thus, recessive risk alleles not present in the C57BL/6J genome will not be detected and mapped under our mouse model.…”

Section: Discussionmentioning

confidence: 99%

“…Fuca1 encodes the lysosomal hydrolase α‐L‐fucosidase implicated in cell growth and signaling . At the chromosome 15 locus, Eif3h, encoding the eukaryotic translation initiation factor, is a candidate that is involved in the cell cycle . One limitation of our study is that all F1 mice carry one chromosome from C57BL/6J and one chromosome from the HMDP.…”

Section: Discussionmentioning

confidence: 99%

The Genetic Architecture of Diet‐Induced Hepatic Fibrosis in Mice

Hui

Kurt

Tuominen³

et al. 2018

Hepatology

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We report the genetic analysis of a "humanized" hyperlipidemic mouse model for progressive nonalcoholic steatohepatitis (NASH) and fibrosis. Mice carrying transgenes for human apolipoprotein E*3-Leiden and cholesteryl ester transfer protein and fed a "Western" diet were studied on the genetic backgrounds of over 100 inbred mouse strains. The mice developed hepatic inflammation and fibrosis that was highly dependent on genetic background, with vast differences in the degree of fibrosis. Histological analysis showed features characteristic of human NASH, including macrovesicular steatosis, hepatocellular ballooning, inflammatory foci, and pericellular collagen deposition. Time course experiments indicated that while hepatic triglyceride levels increased steadily on the diet, hepatic fibrosis occurred at about 12 weeks. We found that the genetic variation predisposing to NASH and fibrosis differs markedly from that predisposing to simple steatosis, consistent with a multistep model in which distinct genetic factors are involved. Moreover, genome-wide association identified distinct genetic loci contributing to steatosis and NASH. Finally, we used hepatic expression data from the mouse panel and from 68 bariatric surgery patients with normal liver, steatosis, or NASH to identify enriched biological pathways. Conclusion: The pathways showed substantial overlap between our mouse model and the human disease.

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“…To our knowledge, this is the first description of a germline CNV involving EIF3H gene. Indeed, only somatic copy number gains and over‐expression of this gene in several cancers were reported . While EIF3H somatic mutations/deletions are rare in tumors, COSMIC database registers copy‐number gains in more than 700 samples and over‐expression in more than 1.300 samples including colon, liver, ovary, breast, eye and central nervous system tumors.…”

Section: Resultsmentioning

confidence: 99%

Germline mutations and new copy number variants among 40 pediatric cancer patients suspected for genetic predisposition

et al. 2019

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Cancer predisposition syndromes (CPS) result from germline pathogenic variants, and they are increasingly recognized in the etiology of many pediatric cancers. Herein, we report the genetic/genomic analysis of 40 pediatric patients enrolled from 2016 to 2018. Our diagnostic workflow was successful in 50% of screened cases. Overall, the proportion of CPS in our case series is 10.9% (20/184) of enrolled patients. Interestingly, 12.5% of patients achieved a conclusive diagnosis through the analysis of chromosomal imbalance. Indeed, we observed germline microdeletions/duplications of regions encompassing cancer‐related genes in 50% of patients undergoing array‐CGH: EIF3H duplication in a patient with infantile desmoplastic astrocytoma and low‐grade Glioma; SLFN11 deletion, SOX4 duplication, and PARK2 partial deletion in three neuroblastoma patients; a PTPRD partial deletion in a child diagnosed with glioblastoma multiforme. Finally, we identified two cases due to DICER1 germline mutations.

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Elevated expression of eukaryotic translation initiation factor 3H is associated with proliferation, invasion and tumorigenicity in human hepatocellular carcinoma

Cited by 35 publications

References 26 publications

A harmine-derived beta-carboline displays anti-cancer effects in vitro by targeting protein synthesis

A harmine-derived beta-carboline displays anti-cancer effects in vitro by targeting protein synthesis

The Genetic Architecture of Diet‐Induced Hepatic Fibrosis in Mice

Germline mutations and new copy number variants among 40 pediatric cancer patients suspected for genetic predisposition

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