In this study,we investigated the functional role of eukaryotic initiation factor 5B(EIF5B)in hepatocellular carcinoma(HCC)and the underlying mechanisms.Bioinformatics analysis demonstrated that the EIF5B transcript a...In this study,we investigated the functional role of eukaryotic initiation factor 5B(EIF5B)in hepatocellular carcinoma(HCC)and the underlying mechanisms.Bioinformatics analysis demonstrated that the EIF5B transcript and protein levels as well as the EIF5Bcopy number were significantly higher in the HCC tissues compared with the non-cancerous liver tissues.Down-regulation of EIF5B significantly decreased proliferation and invasiveness of the HCC cells.Furthermore,EIF5B knockdown suppressed epithelial-mesenchymal transition(EMT)and the cancer stem cell(CSC)phenotype.Down-regulation of EIF5B also increased the sensitivity of HCC cells to 5-fluorouracil(5-FU).In the HCC cells,activation of the NF-kappa B signaling pathway and IkB phosphorylation was significantly reduced by EIF5B silencing.IGF2BP3 increased the stability of the EIF5B mRNA in an m6A-dependent manner.Our data suggested that EIF5B is a promising prognostic biomarker and therapeutic target in HCC.展开更多
Objective:This study investigates the efficacy and mechanisms of Qingjie Fuzheng Granules(QFG)in inhibiting colitis-associated colorectal cancer(CAC)development via RNA sequencing(RNA-seq)and16S ribosomal RNA(rRNA)cor...Objective:This study investigates the efficacy and mechanisms of Qingjie Fuzheng Granules(QFG)in inhibiting colitis-associated colorectal cancer(CAC)development via RNA sequencing(RNA-seq)and16S ribosomal RNA(rRNA)correlation analysis.Methods:CAC was induced in BALB/c mice using azoxymethane(AOM)and dextran sulfate sodium(DSS),and QFG was administered orally to the treatment group.The effects of QFG on CAC were evaluated using disease index,histology,and serum T-cell ratios.RNA-seq and 16S rRNA analysis assessed the transcriptome and microbiome change.Key pharmacodynamic pathways were identified by integrating these data and confirmed via Western blotting and immunofluorescence.The link between microbiota and CACrelated markers was explored using linear discriminant analysis effect size and Spearman correlation analysis.Results:Long-term treatment with QFG prevented AOM/DSS-induced CAC formation,reduced levels of interleukin(IL)-1βtumor necrosis factor-alpha(TNF-α),IL-6,and interferon y(IFN-y),and increased CD3^(+)and CD4^(+)/CD8^(+)T cells ratio,without causing hepatic or renal toxicity.A 16S rRNA analysis revealed that QFG rebalanced the Firmicutes/Bacteroidetes ratio and mitigated AOM/DSS-induced microbiota disturbances.Transcriptomics and Western blotting analysis identified the nucleotide-binding oligomerization domain-containing protein 2(NOD2)/nuclear factor kappa-B(NF-κB)pathway as key for QFG's treatment against CAC.Furthermore,QFG decreased the abundance of Bacilli,Bacillales,Staphylococcaceae,Staphylococcus,Lactobacillales,Aerococcus,Alloprevotella,and Akkermansia,while increasing Clostridiales,Lachnospiraceae,LachnospiraceaeNK4A136group,Ruminococcaceae,and Muribaculaceae,which were highly correlated with CAC-related markers or NOD2/NF-kB pathway.Conclusion:By mapping the relationships between CAC,immune responses,microbiota,and key pathways,this study clarifies the mechanism of QFG in inhibiting CAC,highlighting its potential for clinical use as preventive therapy.展开更多
基金supported by National Natural Science Foundation of China(No.81773167)Project of Traditional Chinese Medicine of Guangdong Administration(No.20132155)Medical and Health Science and Technology Project of Guangzhou Baiyun District(No.2020-YL-002).
文摘In this study,we investigated the functional role of eukaryotic initiation factor 5B(EIF5B)in hepatocellular carcinoma(HCC)and the underlying mechanisms.Bioinformatics analysis demonstrated that the EIF5B transcript and protein levels as well as the EIF5Bcopy number were significantly higher in the HCC tissues compared with the non-cancerous liver tissues.Down-regulation of EIF5B significantly decreased proliferation and invasiveness of the HCC cells.Furthermore,EIF5B knockdown suppressed epithelial-mesenchymal transition(EMT)and the cancer stem cell(CSC)phenotype.Down-regulation of EIF5B also increased the sensitivity of HCC cells to 5-fluorouracil(5-FU).In the HCC cells,activation of the NF-kappa B signaling pathway and IkB phosphorylation was significantly reduced by EIF5B silencing.IGF2BP3 increased the stability of the EIF5B mRNA in an m6A-dependent manner.Our data suggested that EIF5B is a promising prognostic biomarker and therapeutic target in HCC.
基金supported by the National Natural Science Foundation of China(No.82204925)the Financial Project of Fujian Province(No.X2024004)the Natural Science Foundation of Fujian Province,China(No.2024J01782,2022J01368)。
文摘Objective:This study investigates the efficacy and mechanisms of Qingjie Fuzheng Granules(QFG)in inhibiting colitis-associated colorectal cancer(CAC)development via RNA sequencing(RNA-seq)and16S ribosomal RNA(rRNA)correlation analysis.Methods:CAC was induced in BALB/c mice using azoxymethane(AOM)and dextran sulfate sodium(DSS),and QFG was administered orally to the treatment group.The effects of QFG on CAC were evaluated using disease index,histology,and serum T-cell ratios.RNA-seq and 16S rRNA analysis assessed the transcriptome and microbiome change.Key pharmacodynamic pathways were identified by integrating these data and confirmed via Western blotting and immunofluorescence.The link between microbiota and CACrelated markers was explored using linear discriminant analysis effect size and Spearman correlation analysis.Results:Long-term treatment with QFG prevented AOM/DSS-induced CAC formation,reduced levels of interleukin(IL)-1βtumor necrosis factor-alpha(TNF-α),IL-6,and interferon y(IFN-y),and increased CD3^(+)and CD4^(+)/CD8^(+)T cells ratio,without causing hepatic or renal toxicity.A 16S rRNA analysis revealed that QFG rebalanced the Firmicutes/Bacteroidetes ratio and mitigated AOM/DSS-induced microbiota disturbances.Transcriptomics and Western blotting analysis identified the nucleotide-binding oligomerization domain-containing protein 2(NOD2)/nuclear factor kappa-B(NF-κB)pathway as key for QFG's treatment against CAC.Furthermore,QFG decreased the abundance of Bacilli,Bacillales,Staphylococcaceae,Staphylococcus,Lactobacillales,Aerococcus,Alloprevotella,and Akkermansia,while increasing Clostridiales,Lachnospiraceae,LachnospiraceaeNK4A136group,Ruminococcaceae,and Muribaculaceae,which were highly correlated with CAC-related markers or NOD2/NF-kB pathway.Conclusion:By mapping the relationships between CAC,immune responses,microbiota,and key pathways,this study clarifies the mechanism of QFG in inhibiting CAC,highlighting its potential for clinical use as preventive therapy.
基金supported by the National Key R&D Program of China(2019YFA0906003)the National Natural Science Foundation of China(32000989)+5 种基金China Postdoctoral Science Foundation Grant(2020M682911 and 2020M670051ZX)Guangdong Special Support Program(2021JC06Y578)the Shenzhen Municipal Government of China(JCYJ20200109120016553,CJGJZD20200617102403009,and RCBS20210706092256081)the Sanming Project of Shenzhen Health and Family Planning Commission(SZSM202011017)Shenzhen Institute of Synthetic Biology Scientific Research Program(ZTXM20214005)the Shenzhen High-level Hospital Construction Fund。
