We recently report that the expression of polycomb chromobox 4(Cbx4)is significantly correlated with the overall survival of a great cohort of hepatocellular carcinoma(HCC)patients and it enhances hypoxia-induced vasc...We recently report that the expression of polycomb chromobox 4(Cbx4)is significantly correlated with the overall survival of a great cohort of hepatocellular carcinoma(HCC)patients and it enhances hypoxia-induced vascular endothelial growth factor(VEGF)expression and angiogenesis in HCC cells through enhancing sumoylation of hypoxia inducible factor-1alpha(HIF-1α).Here we continue to investigate the potential effects of Cbx4 on the migration and metastasis of the metastatic HCC cell line MHCC97L.Our results show that Cbx4 overexpression in the cell line increases the in vitro vessel formation of vascular endothelial cells in its SUMO interaction motifs-dependent manner,and promotes the in vitro migration of the cancer cell,which can be effectively abrogated by anti-VEGF antibody.Although Cbx4 expression does not impact the in vitro growth of MHCC97L cells,it still promotes the progression and metastasis of orthotopically transplanted tumors in nude mice.These results further support the role of Cbx4 as a SUMO E3 ligase in the progression and metastasis of HCC.展开更多
Introduction:Hepatocellular carcinoma(HCC),a prevalent malignancy,poses significant challenges with high tumor heterogeneity and poor prognosis.MicroRNAs(miRNAs)play a pivotal role in hepatocarcinogenesis.Although abno...Introduction:Hepatocellular carcinoma(HCC),a prevalent malignancy,poses significant challenges with high tumor heterogeneity and poor prognosis.MicroRNAs(miRNAs)play a pivotal role in hepatocarcinogenesis.Although abnormalities in microRNA-557(miR-557)expression have been implicated in various cancer types,its role in HCC remains unclear.Therefore,there is a need to explore the function of microRNA-557 in HCC.Methods:Candidate miRNAs were identified through screening in GSE108724 and GSE20077.Real-time PCR was employed to analyze the expression level of miR-557 in hepatoma cell lines and tissues.Cell viability and migration assays were applied to assess the impact of miR-557 on HCC cell lines.Furthermore,the miR-557 target was predicted through three algorithms(Targetscan,miRWalk,and miRanda),and this was confirmed through luciferase assay and Western blotting.Results:In this study,miR-557 was identified in two datasets and expressed at a low level in both hepatoma cell lines and tissues.Notably,high expression of miR-557 in HCC cells inhibited oncogenesis.Conversely,low expression of miR-557 enhanced tumor proliferation and migration.Polycomb chromobox 4(CBX4)was identified as a direct target of miR-557.Silencing CBX4 influenced the functional impact of miR-557 on HCC cell migration.Conclusion:Taken together,our study contributed to elucidating the hepatoma molecular heterogeneity and provided novel insights into miR-557 role and its target CBX4 in HCC,suggesting its potential as a future effectively druggable target for HCC intervention.展开更多
Gastric cancer(GC)is one of the most common malignancies,with an everincreasing incidence and high mortality rate.Chromobox4(CBX4),also named hPC2,is a small ubiquitin-related modifier(SUMO)E3 ligase.Previous studies ...Gastric cancer(GC)is one of the most common malignancies,with an everincreasing incidence and high mortality rate.Chromobox4(CBX4),also named hPC2,is a small ubiquitin-related modifier(SUMO)E3 ligase.Previous studies have found that high CBX4 expression is associated with tumor size,pathologic differentiation and decreased patient survival in hepatocellular carcinoma(HCC).However,the expression and prognostic value of CBX4 in GC have not been clarified.In our study,ONCOMINE,UALCAN,KaplanMeier Plotter,cBioPortal,DAVID 6.8 and TIMER were utilized.RT-PCR,immunohistochemistry(IHC),Western blot,CCK-8 assay,cell apoptosis assay,cell cycle assay were used to further verify in GC tissue samples or cell line.The transcriptional and protein level of CBX4 in GC tissues was found significantly elevated and a significant association between the expression of CBX4 and clinicopathological parameters was found in GC patients.Low expression of CBX4 in GC patients were correlated with a significantly improved prognosis.The functions of CBX4 are primarily related to the stem cell pluripotency signaling pathway,Hippo signaling pathway,HTLV-I infection,Notch signaling pathway,and N-glycan biosynthesis.Our results may provide novel insights for the selection of therapeutic targets and prognostic biomarkers for GC.展开更多
基金supported by the National Natural Science Foundation of China (91213304,31101044)Shanghai Science and Technology Committee (11JC1406800)Shanghai Committee of Education
文摘We recently report that the expression of polycomb chromobox 4(Cbx4)is significantly correlated with the overall survival of a great cohort of hepatocellular carcinoma(HCC)patients and it enhances hypoxia-induced vascular endothelial growth factor(VEGF)expression and angiogenesis in HCC cells through enhancing sumoylation of hypoxia inducible factor-1alpha(HIF-1α).Here we continue to investigate the potential effects of Cbx4 on the migration and metastasis of the metastatic HCC cell line MHCC97L.Our results show that Cbx4 overexpression in the cell line increases the in vitro vessel formation of vascular endothelial cells in its SUMO interaction motifs-dependent manner,and promotes the in vitro migration of the cancer cell,which can be effectively abrogated by anti-VEGF antibody.Although Cbx4 expression does not impact the in vitro growth of MHCC97L cells,it still promotes the progression and metastasis of orthotopically transplanted tumors in nude mice.These results further support the role of Cbx4 as a SUMO E3 ligase in the progression and metastasis of HCC.
文摘Introduction:Hepatocellular carcinoma(HCC),a prevalent malignancy,poses significant challenges with high tumor heterogeneity and poor prognosis.MicroRNAs(miRNAs)play a pivotal role in hepatocarcinogenesis.Although abnormalities in microRNA-557(miR-557)expression have been implicated in various cancer types,its role in HCC remains unclear.Therefore,there is a need to explore the function of microRNA-557 in HCC.Methods:Candidate miRNAs were identified through screening in GSE108724 and GSE20077.Real-time PCR was employed to analyze the expression level of miR-557 in hepatoma cell lines and tissues.Cell viability and migration assays were applied to assess the impact of miR-557 on HCC cell lines.Furthermore,the miR-557 target was predicted through three algorithms(Targetscan,miRWalk,and miRanda),and this was confirmed through luciferase assay and Western blotting.Results:In this study,miR-557 was identified in two datasets and expressed at a low level in both hepatoma cell lines and tissues.Notably,high expression of miR-557 in HCC cells inhibited oncogenesis.Conversely,low expression of miR-557 enhanced tumor proliferation and migration.Polycomb chromobox 4(CBX4)was identified as a direct target of miR-557.Silencing CBX4 influenced the functional impact of miR-557 on HCC cell migration.Conclusion:Taken together,our study contributed to elucidating the hepatoma molecular heterogeneity and provided novel insights into miR-557 role and its target CBX4 in HCC,suggesting its potential as a future effectively druggable target for HCC intervention.
基金This project was supported by the National Natural Science Foundation of China[grant number 81972655]the Program for Young Eastern Scholars at the Shanghai Institutions of Higher Learning[grant number QD2016004]+1 种基金the Shanghai Science and Technology Commission Research Project[grant number 14441903103]Shanghai Municipal Key Clinic Specialty.
文摘Gastric cancer(GC)is one of the most common malignancies,with an everincreasing incidence and high mortality rate.Chromobox4(CBX4),also named hPC2,is a small ubiquitin-related modifier(SUMO)E3 ligase.Previous studies have found that high CBX4 expression is associated with tumor size,pathologic differentiation and decreased patient survival in hepatocellular carcinoma(HCC).However,the expression and prognostic value of CBX4 in GC have not been clarified.In our study,ONCOMINE,UALCAN,KaplanMeier Plotter,cBioPortal,DAVID 6.8 and TIMER were utilized.RT-PCR,immunohistochemistry(IHC),Western blot,CCK-8 assay,cell apoptosis assay,cell cycle assay were used to further verify in GC tissue samples or cell line.The transcriptional and protein level of CBX4 in GC tissues was found significantly elevated and a significant association between the expression of CBX4 and clinicopathological parameters was found in GC patients.Low expression of CBX4 in GC patients were correlated with a significantly improved prognosis.The functions of CBX4 are primarily related to the stem cell pluripotency signaling pathway,Hippo signaling pathway,HTLV-I infection,Notch signaling pathway,and N-glycan biosynthesis.Our results may provide novel insights for the selection of therapeutic targets and prognostic biomarkers for GC.
