AIM:To study the expression of eukaryotic translation initiation factor 4E(eIF4E),which is closely correlated with malignant tumors,and its relationship to prognosis in hepatocellular carcinoma. METHODS:Western blotti...AIM:To study the expression of eukaryotic translation initiation factor 4E(eIF4E),which is closely correlated with malignant tumors,and its relationship to prognosis in hepatocellular carcinoma. METHODS:Western blotting was performed to quantify the elF4E protein expression in the normal human liver cell line L02 and the hepatoma cell lines Hep3B, HepG2,and Huh7.Forty-six hepatocellular carcinoma samples with complete clinical data were obtained from Changzheng Hospital during the period of December 2008 to July 2009.The expression of eIF4E in the tumor samples and their adjacent tissues were detected by immunohistochemistry.The relationship between the test results and hepatocellular carcinoma(HCC) prognosis was statistically analysed by using a COX proportional hazard model. RESULTS:Western blotting analysis showed that there were distinct eIF4E protein bands in all three of the hepatoma cell lines.In particular,the HepG2 cell line had the highest level of eIF4E protein expression.The L02 cell group had a low eIF4E expression.Immunohistochemical assay showed that there were 32 cases in which the tumour tissue expression was higher than their adjacent tissues,accounting for 69.57%.There were also 14 cases in which the tumour tissue expression was lower or no significant difference was found, accounting for 30.43%.COX proportional hazards model analysis showed that HCC prognosis was related to the depth of invasion,the overexpression of eIF4E and p53, possibly as independent HCC prognostic predictors. CONCLUSION:In summary,eIF4E expression is associated with liver cancer,and patients with high eIF4E expression levels have a higher risk of recurrence.展开更多
The relationship between angiogenesis and eukaryotic translation initiation factor 4E （EIF4E） expression level in non Hodgkin lymphoma （NHL） was studied. Mean microvessel density （MVD） and EIF4E were detected in...The relationship between angiogenesis and eukaryotic translation initiation factor 4E （EIF4E） expression level in non Hodgkin lymphoma （NHL） was studied. Mean microvessel density （MVD） and EIF4E were detected in 52 lymph node samples paraffin sections of patients with newly diagnosed NHL by the way of immunohistochemistry. Antisense EIF4E cDNA was cloned into plasmid pcDNA3.1 （＋） and transfected into Raji cells. A series of angiogenesis related factors,including vascular endothelial growth factor （VEGF）, matrix metalloproteinases 9 （MMP-9） and tissue inhibitor of metalloproteinases-2 （TIMP-2） proteins were detected by Western blot. The results showed that： （1） The Expression of EIF4E and MVD was higher in aggressive lymphomas than in indolent lymphomas（P〈0.05）and the expression of EIF4E was positively correlated with MVD in lymph node of NHL（r=0. 695, P〈0.01）. （2） Antisense EIF4E eukaryocytic expression vector （pcDNA3. 1-EIF4Eas） was constructed successfully. （3） EIF4E, VEGF and MMP-9 were expressed at high levels in Raji cells as compared to normal human peripheral blood monocular cells （NHPMC）, and blockage of EIF4E expression brought down the expression of VEGF and MMP-9. However, TIMP-2 was undetectable in Rail cells, although a moderate level of TIMP-2 was detected in NHPMC. It was concluded that the increased EIF4E expression was associated with aggressive property of NHL.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
Characterization of genes related to sweetpotato viral disease resistance is critical for understanding plant-pathogen interactions, especially with feathery mottle virus infection. For example, genes encoding eukaryo...Characterization of genes related to sweetpotato viral disease resistance is critical for understanding plant-pathogen interactions, especially with feathery mottle virus infection. For example, genes encoding eukaryotic translation initiation factor (eIF)4E, its isoforms, eIF(iso)4E, and the cap-binding protein (CBP) in plants, have been implicated in viral infections aside from their importance in protein synthesis. Full-length cDNA encoding these putative eIF targets from susceptible/resistant and unknown hexaploid sweetpotato (Ipomoea batatas L. Lam) were amplified based on primers designed from the diploid wild-type relative Ipomoea trifida consensus sequences, and designated IbeIF4E, IbeIF(iso)4E and IbCBP. Comparative analyses following direct-sequencing of PCR-amplified cDNAs versus the cloned cDNA sequences identified multiple homeoalleles: one to four IbeIF4E, two to three IbeIF(iso)4E, and two IbCBP within all cultivars tested. Open reading frames were in the length of 696 bp IbeIF4E, 606 bp IbeIF(iso)4E, and 675 bp IbCBP. The encoded single polypeptide lengths were 232, 202, and 225 amino acids for IbeIF4E, IbeIF(iso)4E, and IbCBP, with a calculated protein molecular mass of 26 kDa, 22.8 kDa, and 25.8 kDa, while their theoretical isoelectric points were 5.1, 5.57, and 6.6, respectively. Although the homeoalleles had similar sequence lengths, single nucleotide polymorphisms and multi-allelic variations were detected within the coding sequences. The multi-sequence alignment performed revealed a 66.9% - 96.7% sequence similarity between the predicted amino acid sequences obtained from the homeoalleles and closely related species. Furthermore, phylogenetic analysis revealed ancestral relationships between the eIF4E homeoalleles and other species. The outcome herein on the eIF4E superfamily and its correlation in sequence variations suggest opportunities to decipher the role of eIF4E in hexaploid sweetpotato feathery mottle virus infection.展开更多
BACKGROUND Breast cancer(BC) remains a public health problem. Tamoxifen(TAM) resistance has caused great difficulties for treatment of BC patients. Eukaryotic translation initiation factor 4E binding protein 1(EIF4EBP...BACKGROUND Breast cancer(BC) remains a public health problem. Tamoxifen(TAM) resistance has caused great difficulties for treatment of BC patients. Eukaryotic translation initiation factor 4E binding protein 1(EIF4EBP1) plays critical roles in the tumorigenesis and progression of BC. However, the expression and mechanism of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients are still unclear.AIM To investigate the expression and functions of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients.METHODS High-throughput sequencing data of breast tumors were downloaded from the Gene Expression Omnibus database. Differential gene expression analysis identified EIF4EBP1 to be significantly upregulated in cancer tissues. Its prognostic value was analyzed. The biological function and related pathways of EIF4EBP1 was analyzed. Subsequently, the expression of EIF4EBP1 was determined by real-time reverse transcription polymerase chain reaction and western blotting. Cell Counting Kit-8 assays, colony formation assay and wound healing assay were used to understand the phenotypes of function of EIF4EBP1.RESULTS EIF4EBP1 was upregulated in the TAM-resistant cells, and EIF4EBP1 was related to the prognosis of BC patients. Gene Set Enrichment Analysis showed that EIF4EBP1 might be involved in Hedgehog signaling pathways. Decreasing the expression of EIF4EBP1 could reverse TAM resistance, whereas overexpression of EIF4EBP1 promoted TAM resistance.CONCLUSION This study indicated that EIF4EBP1 was overexpressed in the BC and TAM-resistant cell line, which increased cell proliferation, invasion, migration and TAM resistance in BC cells.展开更多
Objective: To study the prognostic value of the pathological margin and molecular margin marked by eIF4E and P53 protein in laryngeal carcinoma. Methods: The prognostic value of pathological and molecular margin was s...Objective: To study the prognostic value of the pathological margin and molecular margin marked by eIF4E and P53 protein in laryngeal carcinoma. Methods: The prognostic value of pathological and molecular margin was studied in 253 cases and 67 cases respectively, the latter were pathological negative margin chosen from the former. Immunohistochemisty was used to detect the expression of eIF4E and p53 proteins. Results: The rate of pathological, p53 and eIF4E positive margins was 20.2%, 19.4% and 32.8% respectively. The recurrent rate of those with positive margins was higher than that of negative margins, which including pathological margin (70.6% vs 35.1%, P =0.0000), p53 margin (69.2% vs 33.3%, P =0.018) and eIF4E margin (63.6% vs 28.9%, P =0.018); The survival rate of those with negative margins was higher than those with positive margins, including pathological margin (the 5-year cumulative survival rate was 37.52% and 64.37% respectively, P =0.0023), p53 margin (the 5-year cumulative survival rate was 24.62% and 75.69% respectively, P =0.0012) and eIF4E margin (the 5-year cumulative survival rate was 43.31% and 77.52% respectively, P =0.0006). Conclusion: The prognosis of those with both pathological and molecular positive margins was worse than that of the negative margins; Both the eIF4E and p53 were useful markers to pick out the poor prognostic patients from those with pathological negative margin, and the former seemed to be more potential.展开更多
In eukaryotic cells, protein synthesis is a complex and multi-step process that has several mechanisms to start the translation including cap-dependent and cap-independent initiation. The translation control of eukary...In eukaryotic cells, protein synthesis is a complex and multi-step process that has several mechanisms to start the translation including cap-dependent and cap-independent initiation. The translation control of eukaryotic gene expression occurs principally at the initiation step. In this context, it is critical that the eukaryotic translation initiation factor eIF4E bind to the 7-methylguanosine （m7G） cap present at the 5＇- UTRs of most eukaryotic mRNAs. Combined with other initiation factors, elF4E mediates the mRNA recruitment on ribosomes to start the translation. Moreover, the eIF4E nuclear bodies are involved in the export of specific mRNAs from the nucleus to the cytoplasm. In this review, we focus on the elF4E structure and its physiological functions, and describe the role of eIF4E in cancer development and progression and the current therapeutic strategies to target eIF4E.展开更多
In recent years, biotechnology has permitted regulation of the expression of endogenous plant genes to improve agronomlcally important traits. Genetic modification of crops has benefited from emerging knowledge of new...In recent years, biotechnology has permitted regulation of the expression of endogenous plant genes to improve agronomlcally important traits. Genetic modification of crops has benefited from emerging knowledge of new genes, especially genes that exhibit novel functions, one of which is eukaryotlc initiation factor 4E （eIF4E）. eIF4E Is one of the most important translation initiation factors Involved in eukaryotic initiation. Recent research has demonstrated that virus resistance mediated by eIF4E and Its isoform elf （Iso）4E occurs in several plant-virus interactions, thus indicating a potential new role for eIF4E/elF（Iso）4E In resistance strategies against plant viruses. In this review, we briefly describe eIF4E activity In plant translation, its potential role, and functions of the eIF4E subfamily In plant-virus interactions. Other initiation factors such as elF4G could also play a role In plant resistance against viruses. Finally, the potential for developing eIF4E-mediated resistance to plant viruses in the future Is discussed. Future research should focus on elucidation of the resistance mechanism and spectrum mediated by eIF4E. Knowledge of a particu- lar plant-virus interaction will help to deepen our understanding of eIF4E and other eukaryotic Initiation factors, and their involvement in virus disease control.展开更多
Objective Cisplatin(CDDP)-based chemotherapy is a first-line,drug regimen for muscle-invasive bladder cancer(BC)and metastatic bladder cancer.Clinically,resistance to CDDP restricts the clinical benefit of some bladde...Objective Cisplatin(CDDP)-based chemotherapy is a first-line,drug regimen for muscle-invasive bladder cancer(BC)and metastatic bladder cancer.Clinically,resistance to CDDP restricts the clinical benefit of some bladder cancer patients.AT-rich interaction domain 1A(ARID1A)gene mutation occurs frequently in bladder cancer;however,the role of CDDP sensitivity in BC has not been studied.Methods We established ARID1A knockout BC cell lines using CRISPR/Cas9 technology.IC50 determination,flow cytometry analysis of apoptosis,and tumor xenograft assays were performed to verify changes in the CDDP sensitivity of BC cells losing ARID1A.qRT-PCR,Western blotting,RNA interference,bioinformatic analysis,and ChIP-qPCR analysis were performed to further explore the potential mechanism of ARID1A inactivation in CDDP sensitivity in BC.Results It was found that ARID1A inactivation was associated with CDDP resistance in BC cells.Mechanically,loss of ARID1A promoted the expression of eukaryotic translation initiation factor 4A3(EIF4A3)through epigenetic regulation.Increased expression of EIF4A3 promoted the expression of hsa_circ_0008399(circ0008399),a novel circular RNA(circRNA)identified in our previous study,which,to some extent,showed that ARID1A deletion caused CDDP resistance through the inhibitory effect of circ0008399 on the apoptosis of BC cells.Importantly,EIF4A3-IN-2 specifically inhibited the activity of EIF4A3 to reduce circ0008399 production and restored the sensitivity of ARID1A inactivated BC cells to CDDP.Conclusion Our research deepens the understanding of the mechanisms of CDDP resistance in BC and elucidates a potential strategy to improve the efficacy of CDDP in BC patients with ARID1A deletion through combination therapy targeting EIF4A3.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
Objective： To investigate the anti-leukemia effect of total saponins of Rubus parvifo/ius L. （TSRP） on K562 cell xenografts in nude mice and the mechanisms of action. Methods： The K562 cell xenografts in nude mice...Objective： To investigate the anti-leukemia effect of total saponins of Rubus parvifo/ius L. （TSRP） on K562 cell xenografts in nude mice and the mechanisms of action. Methods： The K562 cell xenografts in nude mice were established, and then randomly divided into 5 groups, the control group, the cytosine arabinoside group（Am-c） and 3 TSRP groups （20, 40 and 100 mg/kg）. The tumor volume and mass of each group of nude mice were measured and the anti-tumor rates of TSRP were calculated subsequently. The apoptosis status of tumor cells was detected by hematoxylin-eosin （HE） and terminal dexynucleotidyl transferase （TdT）-mediated dUTP nick end labeling （TUNEL） staining analysis. Finally, the activities of apoptosis related signaling of signal transducer and activator of transcription 3 （STAT3）, eukaryotic initiation factor 4E （eIF4E） and B-cell lymphoma-2 （bcl-2） were determined with immunohistochemistry tests. Results： Subcutaneous injection of K562 cells induced tumor formation in nude mice, and the TSRP treated group showed a significant inhibitory effect on tumor formation. The nude mice treated with TSRP showed a significant decrease in tumor growth rate and tumor weight in comparison to the control group （all P〈0.05）. The HE staining and TUNEL assay showed that TSRP induced cell death by apoptosis. The immunohistochemical assay showed down-regulation of the bcl-2 gene in the TSRP treated cells. The phosphorylation levels of elF4E and STAT3 were decreased obviously after the treatment of TSRP. Conclusion： TSRP had an excellent tumor-suppressing effect on K562 cells in the nude mice xenograft model, suggesting that TSPR can be developed as a promising anti-chronic myeloide leukemia drug.展开更多
文摘AIM:To study the expression of eukaryotic translation initiation factor 4E(eIF4E),which is closely correlated with malignant tumors,and its relationship to prognosis in hepatocellular carcinoma. METHODS:Western blotting was performed to quantify the elF4E protein expression in the normal human liver cell line L02 and the hepatoma cell lines Hep3B, HepG2,and Huh7.Forty-six hepatocellular carcinoma samples with complete clinical data were obtained from Changzheng Hospital during the period of December 2008 to July 2009.The expression of eIF4E in the tumor samples and their adjacent tissues were detected by immunohistochemistry.The relationship between the test results and hepatocellular carcinoma(HCC) prognosis was statistically analysed by using a COX proportional hazard model. RESULTS:Western blotting analysis showed that there were distinct eIF4E protein bands in all three of the hepatoma cell lines.In particular,the HepG2 cell line had the highest level of eIF4E protein expression.The L02 cell group had a low eIF4E expression.Immunohistochemical assay showed that there were 32 cases in which the tumour tissue expression was higher than their adjacent tissues,accounting for 69.57%.There were also 14 cases in which the tumour tissue expression was lower or no significant difference was found, accounting for 30.43%.COX proportional hazards model analysis showed that HCC prognosis was related to the depth of invasion,the overexpression of eIF4E and p53, possibly as independent HCC prognostic predictors. CONCLUSION:In summary,eIF4E expression is associated with liver cancer,and patients with high eIF4E expression levels have a higher risk of recurrence.
文摘The relationship between angiogenesis and eukaryotic translation initiation factor 4E （EIF4E） expression level in non Hodgkin lymphoma （NHL） was studied. Mean microvessel density （MVD） and EIF4E were detected in 52 lymph node samples paraffin sections of patients with newly diagnosed NHL by the way of immunohistochemistry. Antisense EIF4E cDNA was cloned into plasmid pcDNA3.1 （＋） and transfected into Raji cells. A series of angiogenesis related factors,including vascular endothelial growth factor （VEGF）, matrix metalloproteinases 9 （MMP-9） and tissue inhibitor of metalloproteinases-2 （TIMP-2） proteins were detected by Western blot. The results showed that： （1） The Expression of EIF4E and MVD was higher in aggressive lymphomas than in indolent lymphomas（P〈0.05）and the expression of EIF4E was positively correlated with MVD in lymph node of NHL（r=0. 695, P〈0.01）. （2） Antisense EIF4E eukaryocytic expression vector （pcDNA3. 1-EIF4Eas） was constructed successfully. （3） EIF4E, VEGF and MMP-9 were expressed at high levels in Raji cells as compared to normal human peripheral blood monocular cells （NHPMC）, and blockage of EIF4E expression brought down the expression of VEGF and MMP-9. However, TIMP-2 was undetectable in Rail cells, although a moderate level of TIMP-2 was detected in NHPMC. It was concluded that the increased EIF4E expression was associated with aggressive property of NHL.
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.
文摘Characterization of genes related to sweetpotato viral disease resistance is critical for understanding plant-pathogen interactions, especially with feathery mottle virus infection. For example, genes encoding eukaryotic translation initiation factor (eIF)4E, its isoforms, eIF(iso)4E, and the cap-binding protein (CBP) in plants, have been implicated in viral infections aside from their importance in protein synthesis. Full-length cDNA encoding these putative eIF targets from susceptible/resistant and unknown hexaploid sweetpotato (Ipomoea batatas L. Lam) were amplified based on primers designed from the diploid wild-type relative Ipomoea trifida consensus sequences, and designated IbeIF4E, IbeIF(iso)4E and IbCBP. Comparative analyses following direct-sequencing of PCR-amplified cDNAs versus the cloned cDNA sequences identified multiple homeoalleles: one to four IbeIF4E, two to three IbeIF(iso)4E, and two IbCBP within all cultivars tested. Open reading frames were in the length of 696 bp IbeIF4E, 606 bp IbeIF(iso)4E, and 675 bp IbCBP. The encoded single polypeptide lengths were 232, 202, and 225 amino acids for IbeIF4E, IbeIF(iso)4E, and IbCBP, with a calculated protein molecular mass of 26 kDa, 22.8 kDa, and 25.8 kDa, while their theoretical isoelectric points were 5.1, 5.57, and 6.6, respectively. Although the homeoalleles had similar sequence lengths, single nucleotide polymorphisms and multi-allelic variations were detected within the coding sequences. The multi-sequence alignment performed revealed a 66.9% - 96.7% sequence similarity between the predicted amino acid sequences obtained from the homeoalleles and closely related species. Furthermore, phylogenetic analysis revealed ancestral relationships between the eIF4E homeoalleles and other species. The outcome herein on the eIF4E superfamily and its correlation in sequence variations suggest opportunities to decipher the role of eIF4E in hexaploid sweetpotato feathery mottle virus infection.
文摘BACKGROUND Breast cancer(BC) remains a public health problem. Tamoxifen(TAM) resistance has caused great difficulties for treatment of BC patients. Eukaryotic translation initiation factor 4E binding protein 1(EIF4EBP1) plays critical roles in the tumorigenesis and progression of BC. However, the expression and mechanism of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients are still unclear.AIM To investigate the expression and functions of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients.METHODS High-throughput sequencing data of breast tumors were downloaded from the Gene Expression Omnibus database. Differential gene expression analysis identified EIF4EBP1 to be significantly upregulated in cancer tissues. Its prognostic value was analyzed. The biological function and related pathways of EIF4EBP1 was analyzed. Subsequently, the expression of EIF4EBP1 was determined by real-time reverse transcription polymerase chain reaction and western blotting. Cell Counting Kit-8 assays, colony formation assay and wound healing assay were used to understand the phenotypes of function of EIF4EBP1.RESULTS EIF4EBP1 was upregulated in the TAM-resistant cells, and EIF4EBP1 was related to the prognosis of BC patients. Gene Set Enrichment Analysis showed that EIF4EBP1 might be involved in Hedgehog signaling pathways. Decreasing the expression of EIF4EBP1 could reverse TAM resistance, whereas overexpression of EIF4EBP1 promoted TAM resistance.CONCLUSION This study indicated that EIF4EBP1 was overexpressed in the BC and TAM-resistant cell line, which increased cell proliferation, invasion, migration and TAM resistance in BC cells.
文摘Objective: To study the prognostic value of the pathological margin and molecular margin marked by eIF4E and P53 protein in laryngeal carcinoma. Methods: The prognostic value of pathological and molecular margin was studied in 253 cases and 67 cases respectively, the latter were pathological negative margin chosen from the former. Immunohistochemisty was used to detect the expression of eIF4E and p53 proteins. Results: The rate of pathological, p53 and eIF4E positive margins was 20.2%, 19.4% and 32.8% respectively. The recurrent rate of those with positive margins was higher than that of negative margins, which including pathological margin (70.6% vs 35.1%, P =0.0000), p53 margin (69.2% vs 33.3%, P =0.018) and eIF4E margin (63.6% vs 28.9%, P =0.018); The survival rate of those with negative margins was higher than those with positive margins, including pathological margin (the 5-year cumulative survival rate was 37.52% and 64.37% respectively, P =0.0023), p53 margin (the 5-year cumulative survival rate was 24.62% and 75.69% respectively, P =0.0012) and eIF4E margin (the 5-year cumulative survival rate was 43.31% and 77.52% respectively, P =0.0006). Conclusion: The prognosis of those with both pathological and molecular positive margins was worse than that of the negative margins; Both the eIF4E and p53 were useful markers to pick out the poor prognostic patients from those with pathological negative margin, and the former seemed to be more potential.
文摘In eukaryotic cells, protein synthesis is a complex and multi-step process that has several mechanisms to start the translation including cap-dependent and cap-independent initiation. The translation control of eukaryotic gene expression occurs principally at the initiation step. In this context, it is critical that the eukaryotic translation initiation factor eIF4E bind to the 7-methylguanosine （m7G） cap present at the 5＇- UTRs of most eukaryotic mRNAs. Combined with other initiation factors, elF4E mediates the mRNA recruitment on ribosomes to start the translation. Moreover, the eIF4E nuclear bodies are involved in the export of specific mRNAs from the nucleus to the cytoplasm. In this review, we focus on the elF4E structure and its physiological functions, and describe the role of eIF4E in cancer development and progression and the current therapeutic strategies to target eIF4E.
基金Supported by the Hi-Tech Research and Development Plan （863） of China （2001AA212221） and the National Natural Science Foundation of China （30270914）.
文摘In recent years, biotechnology has permitted regulation of the expression of endogenous plant genes to improve agronomlcally important traits. Genetic modification of crops has benefited from emerging knowledge of new genes, especially genes that exhibit novel functions, one of which is eukaryotlc initiation factor 4E （eIF4E）. eIF4E Is one of the most important translation initiation factors Involved in eukaryotic initiation. Recent research has demonstrated that virus resistance mediated by eIF4E and Its isoform elf （Iso）4E occurs in several plant-virus interactions, thus indicating a potential new role for eIF4E/elF（Iso）4E In resistance strategies against plant viruses. In this review, we briefly describe eIF4E activity In plant translation, its potential role, and functions of the eIF4E subfamily In plant-virus interactions. Other initiation factors such as elF4G could also play a role In plant resistance against viruses. Finally, the potential for developing eIF4E-mediated resistance to plant viruses in the future Is discussed. Future research should focus on elucidation of the resistance mechanism and spectrum mediated by eIF4E. Knowledge of a particu- lar plant-virus interaction will help to deepen our understanding of eIF4E and other eukaryotic Initiation factors, and their involvement in virus disease control.
基金This work was supported by grants from the National Natural Science Foundation of China(No.81974396,No.81874091,No.82072840,and No.82102734)the Natural Science Foundation of Hubei Province(No.2020CFB829)the Health Commission of Hubei Province Scientific Research Project(No.WJ2021F081).
文摘Objective Cisplatin(CDDP)-based chemotherapy is a first-line,drug regimen for muscle-invasive bladder cancer(BC)and metastatic bladder cancer.Clinically,resistance to CDDP restricts the clinical benefit of some bladder cancer patients.AT-rich interaction domain 1A(ARID1A)gene mutation occurs frequently in bladder cancer;however,the role of CDDP sensitivity in BC has not been studied.Methods We established ARID1A knockout BC cell lines using CRISPR/Cas9 technology.IC50 determination,flow cytometry analysis of apoptosis,and tumor xenograft assays were performed to verify changes in the CDDP sensitivity of BC cells losing ARID1A.qRT-PCR,Western blotting,RNA interference,bioinformatic analysis,and ChIP-qPCR analysis were performed to further explore the potential mechanism of ARID1A inactivation in CDDP sensitivity in BC.Results It was found that ARID1A inactivation was associated with CDDP resistance in BC cells.Mechanically,loss of ARID1A promoted the expression of eukaryotic translation initiation factor 4A3(EIF4A3)through epigenetic regulation.Increased expression of EIF4A3 promoted the expression of hsa_circ_0008399(circ0008399),a novel circular RNA(circRNA)identified in our previous study,which,to some extent,showed that ARID1A deletion caused CDDP resistance through the inhibitory effect of circ0008399 on the apoptosis of BC cells.Importantly,EIF4A3-IN-2 specifically inhibited the activity of EIF4A3 to reduce circ0008399 production and restored the sensitivity of ARID1A inactivated BC cells to CDDP.Conclusion Our research deepens the understanding of the mechanisms of CDDP resistance in BC and elucidates a potential strategy to improve the efficacy of CDDP in BC patients with ARID1A deletion through combination therapy targeting EIF4A3.
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Supported by grants from Zhejiang Provincial Administration of Traditional Chinese Medicine(No.2011ZA081,No.2012ZB120,No.2013ZB095 and No.2014ZB089)Hangzhou Medical Science and Technology Plan(No.2012A048)
文摘Objective： To investigate the anti-leukemia effect of total saponins of Rubus parvifo/ius L. （TSRP） on K562 cell xenografts in nude mice and the mechanisms of action. Methods： The K562 cell xenografts in nude mice were established, and then randomly divided into 5 groups, the control group, the cytosine arabinoside group（Am-c） and 3 TSRP groups （20, 40 and 100 mg/kg）. The tumor volume and mass of each group of nude mice were measured and the anti-tumor rates of TSRP were calculated subsequently. The apoptosis status of tumor cells was detected by hematoxylin-eosin （HE） and terminal dexynucleotidyl transferase （TdT）-mediated dUTP nick end labeling （TUNEL） staining analysis. Finally, the activities of apoptosis related signaling of signal transducer and activator of transcription 3 （STAT3）, eukaryotic initiation factor 4E （eIF4E） and B-cell lymphoma-2 （bcl-2） were determined with immunohistochemistry tests. Results： Subcutaneous injection of K562 cells induced tumor formation in nude mice, and the TSRP treated group showed a significant inhibitory effect on tumor formation. The nude mice treated with TSRP showed a significant decrease in tumor growth rate and tumor weight in comparison to the control group （all P〈0.05）. The HE staining and TUNEL assay showed that TSRP induced cell death by apoptosis. The immunohistochemical assay showed down-regulation of the bcl-2 gene in the TSRP treated cells. The phosphorylation levels of elF4E and STAT3 were decreased obviously after the treatment of TSRP. Conclusion： TSRP had an excellent tumor-suppressing effect on K562 cells in the nude mice xenograft model, suggesting that TSPR can be developed as a promising anti-chronic myeloide leukemia drug.
