目的全面地了解和研究鸟氨酸脱羧酶1(ODC1)的生物学功能以及在多种肿瘤中的表达情况。方法利用The Human Protein Atlas、NCBI、Oncomine等数据库对ODC1的蛋白定位、蛋白-蛋白互作网络及在多种癌症中的表达与预后情况进行分析。结果对...目的全面地了解和研究鸟氨酸脱羧酶1(ODC1)的生物学功能以及在多种肿瘤中的表达情况。方法利用The Human Protein Atlas、NCBI、Oncomine等数据库对ODC1的蛋白定位、蛋白-蛋白互作网络及在多种癌症中的表达与预后情况进行分析。结果对通过数据库获取的数据进行分析发现,ODC1主要定位于细胞质与细胞膜,并且存在复杂的蛋白-蛋白互作网络。在多种肿瘤细胞中,ODC1的表达显著高于正常细胞,ODC1高表达癌症患者的预后更差。结论ODC1具有复杂的生物学功能,在多种癌症中处于高表达状态,其高表达也显著影响着癌症患者的预后。因此,本研究旨在为以ODC1为靶点的抗癌作用机制的研究提供理论依据与线索。展开更多
Background:Previous researches mainly focused on whether cancer stem cells exist in diffuse large B-cell lym-phoma(DLBCL).However,subgroups with dismal prognosis and stem cell-like characteristics have been over-looke...Background:Previous researches mainly focused on whether cancer stem cells exist in diffuse large B-cell lym-phoma(DLBCL).However,subgroups with dismal prognosis and stem cell-like characteristics have been over-looked.Methods:Using large scale data(n=2133),we conducted machine learning algorithms to identify a high risk DLBCL subgroup with stem cell-like features,and then investigated the potential mechanisms in shaping this subgroup using transcriptome,genome and single-cell RNA-seq data,and in vitro experiments.Results:We identified a high-risk subgroup(25.6%of DLBCL)with stem cell-like characteristics and dismal prog-nosis.This high-risk group(HRG)was featured by upregulation of key enzyme(ODC1)in polyamine metabolism and cold tumor microenvironment(TME),and had a poor prognosis with lower 3-year overall survival(OS)(54.3%vs.83.6%,P<0.0001)and progression-free survival(PFS)(42.8%vs.74.7%,P<0.0001)rates com-pared to the low-risk group.HRG also exhibited malignant proliferative phenotypes similar to Burkitt lymphoma.Patients with MYC rearrangement,double-hit,double-expressors,or complete remission might have either favor-able or poor prognosis,which could be further distinguished by our risk stratification model.Genomic analysis revealed widespread copy number losses in the chemokine and interferon coding regions 8p23.1 and 9p21.3 in HRG.We identified ODC1 as a therapeutic vulnerability for HRG-DLBCL.Single-cell analysis and in vitro ex-periments demonstrated that ODC1 overexpression enhanced DLBCL cell proliferation and drove macrophage polarization towards the M2 phenotype.Conversely,ODC1 inhibition reduced DLBCL cell proliferation,induced cell cycle arrest and apoptosis,and promoted macrophage polarization towards the M1 phenotype.Finally,we developed a comprehensive database of DLBCL for clinical application.Conclusions:Our study effectively advances the precise risk stratification of DLBCL and reveals that ODC1 and immune-deserted microenvironment jointly shape a group of DLBCL patients with stem cell-like features.Target-ing ODC1 regulates immunotherapies in DLBCL,offering new insights for DLBCL treatment.展开更多
Both viruses and host cells compete for intracellular polyamines for efficient propagation.Currently,how the key polyamine-metabolizing enzymes,including ornithine decarboxylase 1(ODC1)and its antizyme 1(OAZ1),are act...Both viruses and host cells compete for intracellular polyamines for efficient propagation.Currently,how the key polyamine-metabolizing enzymes,including ornithine decarboxylase 1(ODC1)and its antizyme 1(OAZ1),are activated to co-ordinate viral propagation and polyamine biosynthesis remains unknown.Here,we report that the matrix protein of rice stripe mosaic virus(RSMV),a cytorhabdovirus,directly hijacks OAZ1 to ensure the proper assembly of rigid bacilliform non-enveloped virions in leafhopper vector.Viral matrix protein effectively competes with ODC1 to bind to OAZ1,and thus,the ability of OAZ1 to target and mediate the degradation of ODC1 is significantly inhibited during viral propagation,which finally promotes polyamines production.Thus,OAZ1 and ODC1 are activated to synergistically promote viral persistent propagation and polyamine biosynthesis in viruliferous vectors.Our data suggest that it is a novel mechanism for rhabdovirus to exploit OAZ1 for facilitating viral assembly.展开更多
文摘目的全面地了解和研究鸟氨酸脱羧酶1(ODC1)的生物学功能以及在多种肿瘤中的表达情况。方法利用The Human Protein Atlas、NCBI、Oncomine等数据库对ODC1的蛋白定位、蛋白-蛋白互作网络及在多种癌症中的表达与预后情况进行分析。结果对通过数据库获取的数据进行分析发现,ODC1主要定位于细胞质与细胞膜,并且存在复杂的蛋白-蛋白互作网络。在多种肿瘤细胞中,ODC1的表达显著高于正常细胞,ODC1高表达癌症患者的预后更差。结论ODC1具有复杂的生物学功能,在多种癌症中处于高表达状态,其高表达也显著影响着癌症患者的预后。因此,本研究旨在为以ODC1为靶点的抗癌作用机制的研究提供理论依据与线索。
基金supported by grants from the National Natural Science Foundation of China(grant number:82170181)Beijing Natural Science Foundation(grant number:7222027)+4 种基金Beijing Physician Scientist Train-ing Project(grant number:BJPSTP-2024-01)the National Key R&D Program of China(grant number:2022YFF1502000)to Liang Wangthe National Key R&D Program of China(grant number:2022YFF1502000)Beijing Municipal Fund for Distinguished Young Scholars(grant number:JQ22022)to Lin FengHebei province government funding for clinical medical talents training and basic research projects(grant number:361007)to Youchao Jia.
文摘Background:Previous researches mainly focused on whether cancer stem cells exist in diffuse large B-cell lym-phoma(DLBCL).However,subgroups with dismal prognosis and stem cell-like characteristics have been over-looked.Methods:Using large scale data(n=2133),we conducted machine learning algorithms to identify a high risk DLBCL subgroup with stem cell-like features,and then investigated the potential mechanisms in shaping this subgroup using transcriptome,genome and single-cell RNA-seq data,and in vitro experiments.Results:We identified a high-risk subgroup(25.6%of DLBCL)with stem cell-like characteristics and dismal prog-nosis.This high-risk group(HRG)was featured by upregulation of key enzyme(ODC1)in polyamine metabolism and cold tumor microenvironment(TME),and had a poor prognosis with lower 3-year overall survival(OS)(54.3%vs.83.6%,P<0.0001)and progression-free survival(PFS)(42.8%vs.74.7%,P<0.0001)rates com-pared to the low-risk group.HRG also exhibited malignant proliferative phenotypes similar to Burkitt lymphoma.Patients with MYC rearrangement,double-hit,double-expressors,or complete remission might have either favor-able or poor prognosis,which could be further distinguished by our risk stratification model.Genomic analysis revealed widespread copy number losses in the chemokine and interferon coding regions 8p23.1 and 9p21.3 in HRG.We identified ODC1 as a therapeutic vulnerability for HRG-DLBCL.Single-cell analysis and in vitro ex-periments demonstrated that ODC1 overexpression enhanced DLBCL cell proliferation and drove macrophage polarization towards the M2 phenotype.Conversely,ODC1 inhibition reduced DLBCL cell proliferation,induced cell cycle arrest and apoptosis,and promoted macrophage polarization towards the M1 phenotype.Finally,we developed a comprehensive database of DLBCL for clinical application.Conclusions:Our study effectively advances the precise risk stratification of DLBCL and reveals that ODC1 and immune-deserted microenvironment jointly shape a group of DLBCL patients with stem cell-like features.Target-ing ODC1 regulates immunotherapies in DLBCL,offering new insights for DLBCL treatment.
基金supported by funds from the National Natural Science Foundation of China to Taiyun Wei under grant number 31920103014the National Natural Science Foundation of China to Dongsheng Jia under grant number 31970160+1 种基金the National Natural Science Foundation of China to Xiaofeng Zhang under grant number 31871931the Natural Science Foundation of Fujian Province to Dongsheng Jia under grant number 2020 J06015.
文摘Both viruses and host cells compete for intracellular polyamines for efficient propagation.Currently,how the key polyamine-metabolizing enzymes,including ornithine decarboxylase 1(ODC1)and its antizyme 1(OAZ1),are activated to co-ordinate viral propagation and polyamine biosynthesis remains unknown.Here,we report that the matrix protein of rice stripe mosaic virus(RSMV),a cytorhabdovirus,directly hijacks OAZ1 to ensure the proper assembly of rigid bacilliform non-enveloped virions in leafhopper vector.Viral matrix protein effectively competes with ODC1 to bind to OAZ1,and thus,the ability of OAZ1 to target and mediate the degradation of ODC1 is significantly inhibited during viral propagation,which finally promotes polyamines production.Thus,OAZ1 and ODC1 are activated to synergistically promote viral persistent propagation and polyamine biosynthesis in viruliferous vectors.Our data suggest that it is a novel mechanism for rhabdovirus to exploit OAZ1 for facilitating viral assembly.
