目的:探索EIF4A3的表达与高级别浆液性卵巢癌患者临床病理特征和预后的关系,明确其在高级别浆液性卵巢癌发生发展过程中的作用。方法:采用免疫组织化学方法检测EIF4A3在高级别浆液性卵巢癌组织、交界性卵巢肿瘤组织以及正常输卵管组织...目的:探索EIF4A3的表达与高级别浆液性卵巢癌患者临床病理特征和预后的关系,明确其在高级别浆液性卵巢癌发生发展过程中的作用。方法:采用免疫组织化学方法检测EIF4A3在高级别浆液性卵巢癌组织、交界性卵巢肿瘤组织以及正常输卵管组织中的表达情况,分析其表达对高级别浆液性卵巢癌临床病理特征及预后的影响。通过TIMER数据库分析EIF4A3在泛癌中的表达水平。通过Sangerbox工具分析EIF4A3表达在泛癌中的预后情况。通过cBioportal网站分析EIF4A3在卵巢癌组织中基因突变的情况。通过GeneMANIA网站构建与EIF4A3共表达基因网络图,其中与EIF4A3最有关系的5个基因分别为ETF1、CENPX、DDX21、DDX31和JMJD6。结果:EIF4A3在高级别浆液性卵巢癌组织中的表达高于交界性卵巢肿瘤和正常输卵管组织(P P P < 0.05)。结论:EIF4A3在高级别浆液性卵巢癌中高表达,与临床病理特征及不良预后有关,EIF4A3可能参与卵巢癌的发生和发展。展开更多
The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatm...The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatment[1].To conquer this challenge,substantial effort has recently been devoted to seeking out natural compounds on account of their multitarget actions.As a traditional herbal medicine,platycodin D(PD)is the major bioactive monomer derived from Platycodon grandiflorum(P.grandiflorum)and is used as an expectorant for pulmonary disease in Asia[2].展开更多
Turnip mosaic virus(TuMV)constitutes one of the primary diseases affecting Brassica rapa,severely impacting its production and resulting in crop failures in various regions worldwide.Recent research has demonstrated t...Turnip mosaic virus(TuMV)constitutes one of the primary diseases affecting Brassica rapa,severely impacting its production and resulting in crop failures in various regions worldwide.Recent research has demonstrated the significance of plant translation initiation factors,specifically the eIF4E and eIF4G family genes,as essential recessive disease resistance genes.In our study,we conducted evolutionary and gene expression studies,leading us to identify e IF(iso)4E.c as a potential TuMV-resistant gene.Leveraging CRISPR/Cas9 technology,we obtained mutant B.rapa plants with edited eIF(iso)4E.c gene.We confirmed eIF(iso)4E.c confers resistance against TuMV through phenotypic observations and virus content evaluations.Furthermore,we employed ribosome profiling assays on eif(iso)4e.c mutant seedlings to unravel the translation landscape in response to TuMV.Interestingly,we observed a moderate correlation between the fold changes in gene expression at the transcriptional and translational levels(R^(2)=0.729).Comparative analysis of ribosome profiling and RNA-seq data revealed that plant-pathogen interaction,and MAPK signaling pathway-plant pathways were involved in eIF(iso)4E.c-mediated TuMV resistance.Further analysis revealed that sequence features,coding sequence length,and normalized minimal free energy,influenced the translation efficiency of genes.Our study highlights that the loss of e IF(iso)4E.c can result in a highly intricate translation mechanism,acting synergistically with transcription to confer resistance against TuMV.展开更多
Objective Aberrant activating mutations in cyclin-dependent kinases 4 and 6(CDK4/6)are common in various cancers,including gastroesophageal malignancies.Although CDK4/6 inhibitors,such as abemaciclib and palbociclib,h...Objective Aberrant activating mutations in cyclin-dependent kinases 4 and 6(CDK4/6)are common in various cancers,including gastroesophageal malignancies.Although CDK4/6 inhibitors,such as abemaciclib and palbociclib,have been approved for breast cancer treatment,their effectiveness as a monotherapy remains limited for gastroesophageal tumors.The present study explored the underlying mechanism of abemaciclib resistance.Methods Abemaciclib-resistant gastric cancer cell lines were generated,and the phospho-eukaryotic translation initiation factor 4E(p-eIF4E)and eIF4E expression was compared between resistant and parental cell lines.In order to analyze the role of eIF4E in cell resistance,siRNA knockdown was employed.The effectiveness of ribavirin alone and its combination with abemaciclib was evaluated in the gastric cancer xenograft mouse model.Results The upregulation of eIF4E was a common feature in gastric cancer cells exposed to prolonged abemaciclib treatment.Gastric cancer cells with increased eIF4E levels exhibited a better response to eIF4E inhibition,especially those that were resistant to abemaciclib.Ribavirin,which is an approved anti-viral drug,significantly improved the efficacy of abemaciclib,both in vitro and in vivo,by inhibiting eIF4E.Importantly,ribavirin effectively suppressed the abemaciclib-resistant gastric cancer growth in mice without causing toxicity.Conclusion These findings suggest that targeting eIF4E can enhance the abemaciclib treatment for gastric cancer,proposing the potential combination therapy of CDK4/6 inhibitors with ribavirin for advanced gastric cancer.展开更多
文摘目的:探索EIF4A3的表达与高级别浆液性卵巢癌患者临床病理特征和预后的关系,明确其在高级别浆液性卵巢癌发生发展过程中的作用。方法:采用免疫组织化学方法检测EIF4A3在高级别浆液性卵巢癌组织、交界性卵巢肿瘤组织以及正常输卵管组织中的表达情况,分析其表达对高级别浆液性卵巢癌临床病理特征及预后的影响。通过TIMER数据库分析EIF4A3在泛癌中的表达水平。通过Sangerbox工具分析EIF4A3表达在泛癌中的预后情况。通过cBioportal网站分析EIF4A3在卵巢癌组织中基因突变的情况。通过GeneMANIA网站构建与EIF4A3共表达基因网络图,其中与EIF4A3最有关系的5个基因分别为ETF1、CENPX、DDX21、DDX31和JMJD6。结果:EIF4A3在高级别浆液性卵巢癌组织中的表达高于交界性卵巢肿瘤和正常输卵管组织(P P P < 0.05)。结论:EIF4A3在高级别浆液性卵巢癌中高表达,与临床病理特征及不良预后有关,EIF4A3可能参与卵巢癌的发生和发展。
基金funded by the National Natural Science Foundation of China(Grant Nos.:82004081 and 52073145)the National Natural Science Foundation of Nanjing University of Chinese Medicine,China(Grant No.:NZY82004081).
文摘The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatment[1].To conquer this challenge,substantial effort has recently been devoted to seeking out natural compounds on account of their multitarget actions.As a traditional herbal medicine,platycodin D(PD)is the major bioactive monomer derived from Platycodon grandiflorum(P.grandiflorum)and is used as an expectorant for pulmonary disease in Asia[2].
基金supported by grants from the Scientist Training Program of BAAFS (Grant No.JKZX202406)the Innovation and Capacity-Building Project of BAAFS (Grant No.KJCX20230221)+2 种基金Collaborative innovation program of the Beijing Vegetable Research Center (Grant No.XTCX202302)the National Natural Science Foundation of China (Grant No.32072567)the China Agriculture Research System of MOF and MARA (Grant No.CARS-A03)。
文摘Turnip mosaic virus(TuMV)constitutes one of the primary diseases affecting Brassica rapa,severely impacting its production and resulting in crop failures in various regions worldwide.Recent research has demonstrated the significance of plant translation initiation factors,specifically the eIF4E and eIF4G family genes,as essential recessive disease resistance genes.In our study,we conducted evolutionary and gene expression studies,leading us to identify e IF(iso)4E.c as a potential TuMV-resistant gene.Leveraging CRISPR/Cas9 technology,we obtained mutant B.rapa plants with edited eIF(iso)4E.c gene.We confirmed eIF(iso)4E.c confers resistance against TuMV through phenotypic observations and virus content evaluations.Furthermore,we employed ribosome profiling assays on eif(iso)4e.c mutant seedlings to unravel the translation landscape in response to TuMV.Interestingly,we observed a moderate correlation between the fold changes in gene expression at the transcriptional and translational levels(R^(2)=0.729).Comparative analysis of ribosome profiling and RNA-seq data revealed that plant-pathogen interaction,and MAPK signaling pathway-plant pathways were involved in eIF(iso)4E.c-mediated TuMV resistance.Further analysis revealed that sequence features,coding sequence length,and normalized minimal free energy,influenced the translation efficiency of genes.Our study highlights that the loss of e IF(iso)4E.c can result in a highly intricate translation mechanism,acting synergistically with transcription to confer resistance against TuMV.
基金supported by the Nature Science Foundation of Hubei Province(No.2017CFB606).
文摘Objective Aberrant activating mutations in cyclin-dependent kinases 4 and 6(CDK4/6)are common in various cancers,including gastroesophageal malignancies.Although CDK4/6 inhibitors,such as abemaciclib and palbociclib,have been approved for breast cancer treatment,their effectiveness as a monotherapy remains limited for gastroesophageal tumors.The present study explored the underlying mechanism of abemaciclib resistance.Methods Abemaciclib-resistant gastric cancer cell lines were generated,and the phospho-eukaryotic translation initiation factor 4E(p-eIF4E)and eIF4E expression was compared between resistant and parental cell lines.In order to analyze the role of eIF4E in cell resistance,siRNA knockdown was employed.The effectiveness of ribavirin alone and its combination with abemaciclib was evaluated in the gastric cancer xenograft mouse model.Results The upregulation of eIF4E was a common feature in gastric cancer cells exposed to prolonged abemaciclib treatment.Gastric cancer cells with increased eIF4E levels exhibited a better response to eIF4E inhibition,especially those that were resistant to abemaciclib.Ribavirin,which is an approved anti-viral drug,significantly improved the efficacy of abemaciclib,both in vitro and in vivo,by inhibiting eIF4E.Importantly,ribavirin effectively suppressed the abemaciclib-resistant gastric cancer growth in mice without causing toxicity.Conclusion These findings suggest that targeting eIF4E can enhance the abemaciclib treatment for gastric cancer,proposing the potential combination therapy of CDK4/6 inhibitors with ribavirin for advanced gastric cancer.
