Eukaryotic initiation factor 5A2(eIF5A2),as one of the two isoforms in the family,is reported to be a novel oncogenic protein that is involved in multiple aspects of many types of human cancer.Overexpression or gene a...Eukaryotic initiation factor 5A2(eIF5A2),as one of the two isoforms in the family,is reported to be a novel oncogenic protein that is involved in multiple aspects of many types of human cancer.Overexpression or gene amplification of EIF5A2 has been demonstrated in many cancers.Accumulated evidence shows that eIF5A2 initiates tumor formation,enhances cancer cell growth,increases cancer cell metastasis,and promotes treatment resistance through multiple means,including inducing epithelial–mesenchymal transition,cytoskeletal rearrangement,angiogenesis,and metabolic reprogramming.Expression of eIF5A2 in cancer correlates with poor survival,advanced disease stage,as well as metastasis,suggesting that eIF5A2 function is crucial for tumor development and maintenance but not for normal tissue homeostasis.All these studies suggest that eIF5A2 is a useful biomarker in the prediction of cancer prognosis and serves as an anticancer molecular target.This review focuses on the expression,subcellular localization,post-translational modifications,and regulatory networks of eIF5A2,as well as its biochemical functions and evolving clinical applications in cancer,especially in human digestive system neoplasms.展开更多
Objective： To study the expression of eukaryotic initiation factor-4E （eIF-4E） and p53 in squamous cell carcinomas （SCC） and to explore their relationship and clinical significance. Methods： The expression of el...Objective： To study the expression of eukaryotic initiation factor-4E （eIF-4E） and p53 in squamous cell carcinomas （SCC） and to explore their relationship and clinical significance. Methods： The expression of elF-4E and p53 in 32 cases of SCC was detected by immunohistochemical SABC method. Results： The positive rate of elF-4E and p53 expression was 93.8% and 56.3% in SCC, and the levels of eIF-4E and p53 were significantly higher in SCC than those in the normal skin tissue （P 〈 0.05）. Conclusion： Both elF-4E and p53 were useful markers in SCC, but the specialty and sensitivity of the eiF- 4E protein was high in SCC.展开更多
Vanishing white matter disease （VWM）, a human atitosomal recessive inherited leukoencephalopathy, is due to mutations in eukaryotic initiation factor 2B （elF2B）. elF2B is responsible for tile initiation of protein...Vanishing white matter disease （VWM）, a human atitosomal recessive inherited leukoencephalopathy, is due to mutations in eukaryotic initiation factor 2B （elF2B）. elF2B is responsible for tile initiation of protein synthesis by its guanine nucleotide exchange lhctor （GEF） activity. Mutations ofelF2B impair GEF activity at different degree. Previous studies implied improperly activated unlblded protein response （UPR） and endoplasmic reticulum stress （ERS） participated in the pathogenesis ofVWM. Autophagy relieves endoplasmic reticulum load by eliminating the unfolded protein. It is still unknown the effects of genotypes on the pathogenesis. In this work, UPR and autophagy flux were analyzed with different mutational types. Methods： ERS tolerance, reflected by apoptosis and cell viability, was detected in human oligodendrocyte cell line transfected with the wild type, or different mutations of p. Argl 13 His, p. Arg269＊ or p. Ser610-Asp613del in el F2 Be. A representative U PR-PERK component of activating transcription lhctor 4 （ATF4） was measured under the basal condition and ERS induction. Autophagy was analyzed the flux in the presence of lysosomal inhibitors. Results： The degree of ERS tolerance varied in different genotypes. The truncated or deletion mutant showed prominent apoptosis cell viability declination after ERS induction. The most seriously damaged GEF activity ofp. Arg269＊ group underwent spontaneous apoptosis. The truncated or deletion mutant showed elevated ATF4 under basal as well as ERS condition. Decreased expression of LC3-1 and LC3-11 in the mutants reflected an impaired autophagy flux, which was more obvious in the truncated or deletion mutants alter ERS induction. Conclusions： GEF activities in dilt;erent genotypes could influence the cell ERS tolerance as well as compensatory pathways of UPR and autophagy. Oligodendrocytes with truncated or deletion inutants showed less tolerable to ERS.展开更多
Objective The expression levels of histone deacetylase 2(HDAC2),eukaryotic initiation factor 5(eIF5),and eukaryotic initiation factor 6(eIF6),and relationship between HDAC2 and eIF5 or eIF6 in lung cancer tissues were...Objective The expression levels of histone deacetylase 2(HDAC2),eukaryotic initiation factor 5(eIF5),and eukaryotic initiation factor 6(eIF6),and relationship between HDAC2 and eIF5 or eIF6 in lung cancer tissues were investigated,in order to charify the relationship between HDAC2 and the prognosis of lung cancer patients and its influence on the expression of eIF5 and eIF6.Methods The expression of HDAC2,eIF5,and eIF6 in lung cancer tissues was detected by quantitative reverse transcription polymerase chain reaction.The expression correlation between HDAC2 and eIF5 or eIF6 was tested using a t test.The correlation between HDAC2 and eIF5 or eIF6 was analyzed using the TCGA database.The identified cells were constructed with small interfering siRNA and HDAC2 overexpression plasmid.The proliferation and migration ability of the identified cells was investigated by CCK8 and Transwell assays,respectively.Results HDAC2,eIF5,and eIF6 were overexpressed in lung cancer tissues,and HDAC2 expression level was negatively correlated with the prognosis of lung cancer patients.HDAC2 expression level was positively correlated with eIF5 and eIF6 expression levels.HDAC2 could regulate the expression of eIF5 and eIF6.The regulation of proliferation and invasion of lung cancer cells by HDAC2 depended on eIF5 and eIF6.Conclusion HDAC2,eIF5,and eIF6 were closely related with lung cancer tumorigenesis,which might be potential biological markers and therapeutic targets for lung cancer.展开更多
Eukaryotic translation initiation factor 5A （eIFSA） is a protein-translation initiation factor in eukaryotic cells. Recent studies found that elFSA plays an important role in regulating the processes of cellular sen...Eukaryotic translation initiation factor 5A （eIFSA） is a protein-translation initiation factor in eukaryotic cells. Recent studies found that elFSA plays an important role in regulating the processes of cellular senescence and death, environmental stress response and immune response in animal and plant cells. In the present study, a cDNA containing the complete amino acid sequence of eIFSA was obtained for the first time by sequencing the Litopenaeus vannamei cDNA library, which contained a 474 bp long open reading frame encoding 157 amino acids, with the predicted molecular weight of about 17. 257 ku and theoretical isoelectric point of 5.06. Comparison analysis showed that the amino acid sequence of elFSA gene in L vannamei shared relatively high homology with that in other species. Real-time quantitative RT-PCR results indicated that the mRNA expression of elFSA gene in different tissues of L. vannamei exhibited no significant difference. Real-time quantitative RT-PCR analysis of L. vannamei hepatopancreas infected with WSSV, TSV and IHHNV showed that the mRNA levels of elFSA gene was re- spectively significantly increased, which was 2.2, 2.5 and 1.6 times of that in control group, indicating that eIFSA may be involved in the antiviral immune response of L. vannamei.展开更多
[Objectives] To study the therapeutic effect and mechanism of New Maixian Powder on ulcerative colitis( UC) rats through observing its regulatory effect on the protein kinase R-like endoplasmic reticulum kinase( PERK)...[Objectives] To study the therapeutic effect and mechanism of New Maixian Powder on ulcerative colitis( UC) rats through observing its regulatory effect on the protein kinase R-like endoplasmic reticulum kinase( PERK)/eukaryotic translation initiation factor-2α( e IF-2α)/nuclear transcription factor-kappa B( NF-κB) signaling pathway. [Methods]First,60 SD rats were randomly divided into normal group,model group,mesalazine group,and New Maixian Powder low,medium and high dose groups,10 rats each group. Then,dextran sulfate sodium( DSS) was used to induce UC rats. The mesalazine group was given 0. 42 g/( kg·d) of mesalazine sustained-release granule suspension,New Maixian Powder low,medium and high dose groups were given 1. 5,3,and 6 g/( kg·d) of New Maixian Powder suspension,respectively,and other groups were given an equal volume of physiological saline,continuous intragastric administration for 14 d. Next,the disease activity index( DAI) of UC rats was evaluated; the expression of NF-κB in serum was measured by enzyme-linked immunosorbent assay( ELISA); the expression of PERK and e IF-2α protein and m RNA in colon tissue was detected by Western blot and real-time quantitative polymerase chain reaction( RT q-PCR). [Results] Compared with the normal group,the DAI score and serum NF-κB level in the model group were significantly higher( P < 0. 05),and PERK and e IF-2α protein and m RNA levels in the colon tissue were increased( P < 0. 05); compared with the model group,the DAI score decreased and serum NF-κB level declined in the New Maixian Powder group,and the expression of PERK and e IF-2α protein and m RNA in New Maixian Powder medium dose and high dose groups declined( P < 0. 05). [Conclusions]New Maixian Powder has good therapeutic effect on UC rats,and its mechanism may be connected with the inhibition of the activation of PERK/e IF-2α/NF-κB signaling pathway.展开更多
Background:Epithelial-mesenchymal transition(EMT) is believed to be the critical process in malignant tumor invasion and metastases,and has a great influence on improving the survival rate in non-small-cell lung cance...Background:Epithelial-mesenchymal transition(EMT) is believed to be the critical process in malignant tumor invasion and metastases,and has a great influence on improving the survival rate in non-small-cell lung cancer(NSCLC) patients.Recent studies suggested that eukaryotic initiation factor 5A-2(eIF5A-2) might serve as an adverse prognostic marker of survival.We detected eIF5A-2 in NSCLC A549 cells,and found that the invasive capability correlates with the eIF5A-2 expression.Methods:Transforming growth factor(TGF)-β1 was used to induce EMT in A549 cells.Western blotting,immunofluorescence,wound healing assay,and transwell-matrigel invasion chambers were used to identify phenotype changes.Western blotting was also used to observe changes of the expression of eIF5A-2.We down-regulated the eIF5A-2 expression using an eIF5A-2 siRNA and identified the phenotype changes by western blotting and immunofluorescence.We tested the change of migration and invasion capabilities of A549 cells by the wound healing assay and transwell-matrigel invasion chambers.Results:After stimulating with TGF-β1,almost all A549 cells changed to the mesenchymal phenotype and acquired more migration and invasion capabilities.These cells also had higher eIF5A-2 protein expression.Down-regulation of eIF5A-2 expression with eIF5A-2 siRNA transfection could change the cells from mesenchymal to epithelial phenotype and decrease tumor cell migration and invasive capabilities significantly.Conclusions:The expression of eIF5A-2 was up-regulated following EMT phenotype changes in A549 cells,which correlated with enhanced tumor invasion and metastatic capabilities.Furthermore,in the A549 cell line,the process of EMT phenotype change could be reversed by eIF5A-2 siRNA,with a consequent weakening of both invasive and metastatic capabilities.展开更多
基金Supported by Natural Science Foundation of Hubei Province,No.2016CFB596Wuhan City Medical Research Project,Nos.WX15B14and WX17Q39Hubei Province Scientific Research Project,No.WJ2015MB137
文摘Eukaryotic initiation factor 5A2(eIF5A2),as one of the two isoforms in the family,is reported to be a novel oncogenic protein that is involved in multiple aspects of many types of human cancer.Overexpression or gene amplification of EIF5A2 has been demonstrated in many cancers.Accumulated evidence shows that eIF5A2 initiates tumor formation,enhances cancer cell growth,increases cancer cell metastasis,and promotes treatment resistance through multiple means,including inducing epithelial–mesenchymal transition,cytoskeletal rearrangement,angiogenesis,and metabolic reprogramming.Expression of eIF5A2 in cancer correlates with poor survival,advanced disease stage,as well as metastasis,suggesting that eIF5A2 function is crucial for tumor development and maintenance but not for normal tissue homeostasis.All these studies suggest that eIF5A2 is a useful biomarker in the prediction of cancer prognosis and serves as an anticancer molecular target.This review focuses on the expression,subcellular localization,post-translational modifications,and regulatory networks of eIF5A2,as well as its biochemical functions and evolving clinical applications in cancer,especially in human digestive system neoplasms.
文摘Objective： To study the expression of eukaryotic initiation factor-4E （eIF-4E） and p53 in squamous cell carcinomas （SCC） and to explore their relationship and clinical significance. Methods： The expression of elF-4E and p53 in 32 cases of SCC was detected by immunohistochemical SABC method. Results： The positive rate of elF-4E and p53 expression was 93.8% and 56.3% in SCC, and the levels of eIF-4E and p53 were significantly higher in SCC than those in the normal skin tissue （P 〈 0.05）. Conclusion： Both elF-4E and p53 were useful markers in SCC, but the specialty and sensitivity of the eiF- 4E protein was high in SCC.
基金grants from the Natural Science Foundation of China，National Key Technology R and D Program，Key Laboratory Program of Ministry of Education
文摘Vanishing white matter disease （VWM）, a human atitosomal recessive inherited leukoencephalopathy, is due to mutations in eukaryotic initiation factor 2B （elF2B）. elF2B is responsible for tile initiation of protein synthesis by its guanine nucleotide exchange lhctor （GEF） activity. Mutations ofelF2B impair GEF activity at different degree. Previous studies implied improperly activated unlblded protein response （UPR） and endoplasmic reticulum stress （ERS） participated in the pathogenesis ofVWM. Autophagy relieves endoplasmic reticulum load by eliminating the unfolded protein. It is still unknown the effects of genotypes on the pathogenesis. In this work, UPR and autophagy flux were analyzed with different mutational types. Methods： ERS tolerance, reflected by apoptosis and cell viability, was detected in human oligodendrocyte cell line transfected with the wild type, or different mutations of p. Argl 13 His, p. Arg269＊ or p. Ser610-Asp613del in el F2 Be. A representative U PR-PERK component of activating transcription lhctor 4 （ATF4） was measured under the basal condition and ERS induction. Autophagy was analyzed the flux in the presence of lysosomal inhibitors. Results： The degree of ERS tolerance varied in different genotypes. The truncated or deletion mutant showed prominent apoptosis cell viability declination after ERS induction. The most seriously damaged GEF activity ofp. Arg269＊ group underwent spontaneous apoptosis. The truncated or deletion mutant showed elevated ATF4 under basal as well as ERS condition. Decreased expression of LC3-1 and LC3-11 in the mutants reflected an impaired autophagy flux, which was more obvious in the truncated or deletion mutants alter ERS induction. Conclusions： GEF activities in dilt;erent genotypes could influence the cell ERS tolerance as well as compensatory pathways of UPR and autophagy. Oligodendrocytes with truncated or deletion inutants showed less tolerable to ERS.
基金supported by the Startup Fund for scientific research,Fujian Medical University(No.2018QH1114)Fujian Health and Healthy Middle-aged and Young Backbone Talents Training Project(No.2019-ZQN-4).
文摘Objective The expression levels of histone deacetylase 2(HDAC2),eukaryotic initiation factor 5(eIF5),and eukaryotic initiation factor 6(eIF6),and relationship between HDAC2 and eIF5 or eIF6 in lung cancer tissues were investigated,in order to charify the relationship between HDAC2 and the prognosis of lung cancer patients and its influence on the expression of eIF5 and eIF6.Methods The expression of HDAC2,eIF5,and eIF6 in lung cancer tissues was detected by quantitative reverse transcription polymerase chain reaction.The expression correlation between HDAC2 and eIF5 or eIF6 was tested using a t test.The correlation between HDAC2 and eIF5 or eIF6 was analyzed using the TCGA database.The identified cells were constructed with small interfering siRNA and HDAC2 overexpression plasmid.The proliferation and migration ability of the identified cells was investigated by CCK8 and Transwell assays,respectively.Results HDAC2,eIF5,and eIF6 were overexpressed in lung cancer tissues,and HDAC2 expression level was negatively correlated with the prognosis of lung cancer patients.HDAC2 expression level was positively correlated with eIF5 and eIF6 expression levels.HDAC2 could regulate the expression of eIF5 and eIF6.The regulation of proliferation and invasion of lung cancer cells by HDAC2 depended on eIF5 and eIF6.Conclusion HDAC2,eIF5,and eIF6 were closely related with lung cancer tumorigenesis,which might be potential biological markers and therapeutic targets for lung cancer.
基金Supported by National Natural Science Foundation of China(31160531)
文摘Eukaryotic translation initiation factor 5A （eIFSA） is a protein-translation initiation factor in eukaryotic cells. Recent studies found that elFSA plays an important role in regulating the processes of cellular senescence and death, environmental stress response and immune response in animal and plant cells. In the present study, a cDNA containing the complete amino acid sequence of eIFSA was obtained for the first time by sequencing the Litopenaeus vannamei cDNA library, which contained a 474 bp long open reading frame encoding 157 amino acids, with the predicted molecular weight of about 17. 257 ku and theoretical isoelectric point of 5.06. Comparison analysis showed that the amino acid sequence of elFSA gene in L vannamei shared relatively high homology with that in other species. Real-time quantitative RT-PCR results indicated that the mRNA expression of elFSA gene in different tissues of L. vannamei exhibited no significant difference. Real-time quantitative RT-PCR analysis of L. vannamei hepatopancreas infected with WSSV, TSV and IHHNV showed that the mRNA levels of elFSA gene was re- spectively significantly increased, which was 2.2, 2.5 and 1.6 times of that in control group, indicating that eIFSA may be involved in the antiviral immune response of L. vannamei.
基金Supported by Science and Technology Program of Zhejiang Province(2016C33085)
文摘[Objectives] To study the therapeutic effect and mechanism of New Maixian Powder on ulcerative colitis( UC) rats through observing its regulatory effect on the protein kinase R-like endoplasmic reticulum kinase( PERK)/eukaryotic translation initiation factor-2α( e IF-2α)/nuclear transcription factor-kappa B( NF-κB) signaling pathway. [Methods]First,60 SD rats were randomly divided into normal group,model group,mesalazine group,and New Maixian Powder low,medium and high dose groups,10 rats each group. Then,dextran sulfate sodium( DSS) was used to induce UC rats. The mesalazine group was given 0. 42 g/( kg·d) of mesalazine sustained-release granule suspension,New Maixian Powder low,medium and high dose groups were given 1. 5,3,and 6 g/( kg·d) of New Maixian Powder suspension,respectively,and other groups were given an equal volume of physiological saline,continuous intragastric administration for 14 d. Next,the disease activity index( DAI) of UC rats was evaluated; the expression of NF-κB in serum was measured by enzyme-linked immunosorbent assay( ELISA); the expression of PERK and e IF-2α protein and m RNA in colon tissue was detected by Western blot and real-time quantitative polymerase chain reaction( RT q-PCR). [Results] Compared with the normal group,the DAI score and serum NF-κB level in the model group were significantly higher( P < 0. 05),and PERK and e IF-2α protein and m RNA levels in the colon tissue were increased( P < 0. 05); compared with the model group,the DAI score decreased and serum NF-κB level declined in the New Maixian Powder group,and the expression of PERK and e IF-2α protein and m RNA in New Maixian Powder medium dose and high dose groups declined( P < 0. 05). [Conclusions]New Maixian Powder has good therapeutic effect on UC rats,and its mechanism may be connected with the inhibition of the activation of PERK/e IF-2α/NF-κB signaling pathway.
基金Project supported by the Natural Science Fundation of Ningbo (No. 2011A610052)the Zhejiang Provincial Natural Science Fundation (No. LY12H16002) of China
文摘Background:Epithelial-mesenchymal transition(EMT) is believed to be the critical process in malignant tumor invasion and metastases,and has a great influence on improving the survival rate in non-small-cell lung cancer(NSCLC) patients.Recent studies suggested that eukaryotic initiation factor 5A-2(eIF5A-2) might serve as an adverse prognostic marker of survival.We detected eIF5A-2 in NSCLC A549 cells,and found that the invasive capability correlates with the eIF5A-2 expression.Methods:Transforming growth factor(TGF)-β1 was used to induce EMT in A549 cells.Western blotting,immunofluorescence,wound healing assay,and transwell-matrigel invasion chambers were used to identify phenotype changes.Western blotting was also used to observe changes of the expression of eIF5A-2.We down-regulated the eIF5A-2 expression using an eIF5A-2 siRNA and identified the phenotype changes by western blotting and immunofluorescence.We tested the change of migration and invasion capabilities of A549 cells by the wound healing assay and transwell-matrigel invasion chambers.Results:After stimulating with TGF-β1,almost all A549 cells changed to the mesenchymal phenotype and acquired more migration and invasion capabilities.These cells also had higher eIF5A-2 protein expression.Down-regulation of eIF5A-2 expression with eIF5A-2 siRNA transfection could change the cells from mesenchymal to epithelial phenotype and decrease tumor cell migration and invasive capabilities significantly.Conclusions:The expression of eIF5A-2 was up-regulated following EMT phenotype changes in A549 cells,which correlated with enhanced tumor invasion and metastatic capabilities.Furthermore,in the A549 cell line,the process of EMT phenotype change could be reversed by eIF5A-2 siRNA,with a consequent weakening of both invasive and metastatic capabilities.
