C-mannosylation is a post-translational modification that occurs intracellularly in the endoplasmic reticulum.In humans,biosynthesis of C-mannosylation in proteins containing thrombospondin type 1 repeat is catalyzed ...C-mannosylation is a post-translational modification that occurs intracellularly in the endoplasmic reticulum.In humans,biosynthesis of C-mannosylation in proteins containing thrombospondin type 1 repeat is catalyzed by the DPY19 family;nonetheless,biological functions of protein C-mannosylation are not yet fully understood,especially in tumor progression.Vasculogenic mimicry(VM)is the formation of fluid-conducting channels by highly invasive and genetically deregulated tumor cells,enabling the tumors to form matrix-embedded vasculogenic structures,containing plasma and blood cells to meet the metabolic demands of rapidly growing tumors.In this study,we focused on DPY19L3,a C-mannosyltransferase,and aimed to unravel its role in VM.Knockout of DPY19L3 inhibited the formation of VM in HT1080 human fibrosarcoma cells.Re-expression of wild-type DPY19L3 recovered VM formation;however,DPY19L3 isoform2,an enzymatic activity-defect mutant,did not restore it,suggesting that the C-mannosyltransferase activity of DPY19L3 is crucial to its function.Furthermore,the knockdown of DPY19L3 in MDA-MB-231 breast cancer cells hindered its network formation ability.Altogether,our findings suggest that DPY19L3 is required for VM formation and stipulate the relevance of C-mannosylation in oncogenesis.展开更多
目的探讨血清甲胎蛋白(alpha fetoprotein,AFP)、甲胎蛋白异质体(alpha fetoprotein-L3,AFP-L3)以及异常凝血酶原又称维生素K缺乏拮抗剂Ⅱ诱导产生的蛋白(protein induced by vitamin K absence or antagonist-Ⅱ,PIVKA-Ⅱ)单独及联合...目的探讨血清甲胎蛋白(alpha fetoprotein,AFP)、甲胎蛋白异质体(alpha fetoprotein-L3,AFP-L3)以及异常凝血酶原又称维生素K缺乏拮抗剂Ⅱ诱导产生的蛋白(protein induced by vitamin K absence or antagonist-Ⅱ,PIVKA-Ⅱ)单独及联合检测在早期原发性肝细胞癌(hepatocellular carcinoma,HCC)中的诊断价值。方法回顾性挑选2021年4月~2022年5月在徐州医科大学附属医院住院或门诊的55例HCC患者作为HCC组,54例肝脏良性病变(benign liver disease,BLD)患者为BLD组,另选取43例健康体检人员为对照组,分别检测3组研究对象的血清AFP、AFP-L3及PIVKA-Ⅱ表达水平,绘制受试者工作特征(receiver operator characteristic,ROC)曲线,分析AFP、AFP-L3及PIVKA-Ⅱ单独及联合检测对HCC的诊断效能。结果HCC组患者血清AFP、AFP-L3及PIVKA-Ⅱ水平明显高于BLD组及对照组,差异有统计学意义(P<0.05),血清AFP、AFP-L3和PIVKA-Ⅱ的表达水平与HCC患者的肿瘤个数、最大径、TNM分期及门静脉癌栓有关,ROC曲线分析显示,HCC患者单独检测AFP、AFP-L3及PIVKA-Ⅱ的曲线下面积分别为0.809、0.828、0.896,联合检测3项指标的曲线下面积最高,为0.937。结论血清AFP、AFP-L3及PIVKA-Ⅱ单独检测均对HCC诊断具有一定的价值,但三者联合检测可提高HCC的诊断效能。展开更多
文摘C-mannosylation is a post-translational modification that occurs intracellularly in the endoplasmic reticulum.In humans,biosynthesis of C-mannosylation in proteins containing thrombospondin type 1 repeat is catalyzed by the DPY19 family;nonetheless,biological functions of protein C-mannosylation are not yet fully understood,especially in tumor progression.Vasculogenic mimicry(VM)is the formation of fluid-conducting channels by highly invasive and genetically deregulated tumor cells,enabling the tumors to form matrix-embedded vasculogenic structures,containing plasma and blood cells to meet the metabolic demands of rapidly growing tumors.In this study,we focused on DPY19L3,a C-mannosyltransferase,and aimed to unravel its role in VM.Knockout of DPY19L3 inhibited the formation of VM in HT1080 human fibrosarcoma cells.Re-expression of wild-type DPY19L3 recovered VM formation;however,DPY19L3 isoform2,an enzymatic activity-defect mutant,did not restore it,suggesting that the C-mannosyltransferase activity of DPY19L3 is crucial to its function.Furthermore,the knockdown of DPY19L3 in MDA-MB-231 breast cancer cells hindered its network formation ability.Altogether,our findings suggest that DPY19L3 is required for VM formation and stipulate the relevance of C-mannosylation in oncogenesis.
文摘目的探讨血清甲胎蛋白(alpha fetoprotein,AFP)、甲胎蛋白异质体(alpha fetoprotein-L3,AFP-L3)以及异常凝血酶原又称维生素K缺乏拮抗剂Ⅱ诱导产生的蛋白(protein induced by vitamin K absence or antagonist-Ⅱ,PIVKA-Ⅱ)单独及联合检测在早期原发性肝细胞癌(hepatocellular carcinoma,HCC)中的诊断价值。方法回顾性挑选2021年4月~2022年5月在徐州医科大学附属医院住院或门诊的55例HCC患者作为HCC组,54例肝脏良性病变(benign liver disease,BLD)患者为BLD组,另选取43例健康体检人员为对照组,分别检测3组研究对象的血清AFP、AFP-L3及PIVKA-Ⅱ表达水平,绘制受试者工作特征(receiver operator characteristic,ROC)曲线,分析AFP、AFP-L3及PIVKA-Ⅱ单独及联合检测对HCC的诊断效能。结果HCC组患者血清AFP、AFP-L3及PIVKA-Ⅱ水平明显高于BLD组及对照组,差异有统计学意义(P<0.05),血清AFP、AFP-L3和PIVKA-Ⅱ的表达水平与HCC患者的肿瘤个数、最大径、TNM分期及门静脉癌栓有关,ROC曲线分析显示,HCC患者单独检测AFP、AFP-L3及PIVKA-Ⅱ的曲线下面积分别为0.809、0.828、0.896,联合检测3项指标的曲线下面积最高,为0.937。结论血清AFP、AFP-L3及PIVKA-Ⅱ单独检测均对HCC诊断具有一定的价值,但三者联合检测可提高HCC的诊断效能。
