目的:探讨双特异性酪氨酸磷酸化调节激酶2(dual-specificity tyrosine phosphorylation-regulated kinase2,DYRK2)在胰腺癌中的表达及其临床意义.方法:应用实时荧光定量PCR、Western blot及免疫组织化学技术检测40例胰腺癌及其癌旁正常...目的:探讨双特异性酪氨酸磷酸化调节激酶2(dual-specificity tyrosine phosphorylation-regulated kinase2,DYRK2)在胰腺癌中的表达及其临床意义.方法:应用实时荧光定量PCR、Western blot及免疫组织化学技术检测40例胰腺癌及其癌旁正常组织标本中DYRK2mRNA和蛋白的表达量,并结合免疫组织化学结果及胰腺癌患者的临床病理资料进行统计学分析.结果:实时荧光定量PCR检测显示,DYRK2m R N A在胰腺癌及其癌旁组织中均有表达,但后者的表达水平明显高于前者(P<0.01);Western blot检测显示,在88.9%的癌组织中D Y R K2蛋白的表达量低于其对应的癌旁组织;免疫组织化学染色显示,DYRK2在胰腺癌组织中的阳性比例明显低于其癌旁组织(42.5%vs87.5%,X2=17.802,P<0.01),且DYRK2的表达与胰腺癌有无淋巴结转移相关(X2=6.32,P<0.05).结论:DYRK2在胰腺癌组织中表达下调,可能与胰腺癌的发生发展和淋巴结转移等恶性生物学行为相关.展开更多
Proteins of the DYRK(dual-specificity tyrosine-phosphorylation-regulated kinase) family are characterized by the presence of a conserved kinase domain and N-terminal DH box.DYRK2 is involved in regulating key developm...Proteins of the DYRK(dual-specificity tyrosine-phosphorylation-regulated kinase) family are characterized by the presence of a conserved kinase domain and N-terminal DH box.DYRK2 is involved in regulating key developmental and cellular processes,such as neurogenesis,cell proliferation,cytokinesis,and cellular differentiation.Herein,we report that the ortholog of DYRK2 found in zebrafish shares about 70% identity with that of human,mouse,and chick.RT-PCR showed that DYRK2 is expressed maternally and zygotically.In-situ hybridization results show that DYRK2 is expressed in somite cells that will develop into muscles.Our results provide preliminary evidence for investigating the in-vivo function of DYRK2 in zebrafish muscle development.展开更多
目的探讨微小RNA622(microRNA-622,miR-622)及双重特异性酪氨酸调节激酶2(DYRK2)在结肠癌组织及结肠细胞系SW1116、SW480中的表达情况并研究其对SW1116侵袭转移能力的影响。方法选取82例结肠癌及癌旁组织标本,培养结肠癌细胞系SW1116、S...目的探讨微小RNA622(microRNA-622,miR-622)及双重特异性酪氨酸调节激酶2(DYRK2)在结肠癌组织及结肠细胞系SW1116、SW480中的表达情况并研究其对SW1116侵袭转移能力的影响。方法选取82例结肠癌及癌旁组织标本,培养结肠癌细胞系SW1116、SW480及正常结肠上皮细胞系NCM460细胞。Real time PCR检测组织及细胞中miR-622的表达,Real time PCR、免疫组织化学、Western blot检测DYRK2基因及蛋白的表达并行Pearson相关性分析。在SW1116中转染miR-622mimics上调miR-622表达,同时对照(NC)组转染阴性序列并验证,Real time PCR及Western blot进一步检测上调miR-622后SW1116中DYRK2基因及蛋白表达水平,同时用Transwell法检测SW1116细胞侵袭转移能力的变化。结果Real time PCR及Western blot结果显示,相比于癌旁组织和正常结肠上皮细胞系NCM460,结肠癌组织及结肠癌细胞SW1116中miR-622mRNA呈高表达而DYRK2mRNA及蛋白呈低表达,两者表达呈明显负相关(r=0.916,P<0.01)。转染miR-622 mimics后,Real time PCR及Western blot结果显示,相比于NC组,miR-622mimics组DYRK2mRNA及蛋白表达水平减低(P<0.01)。相应的,Transwell结果显示,相比于NC组,SW1116细胞转染miR-622mimics后侵袭转移能力明显增强(P<0.01)。结论结肠癌中miR-622呈高表达而DYRK2呈低表达,上调miR-622可负性调控DYRK2表达并促进SW1116细胞侵袭转移。展开更多
Cullin-RING ligases(CRLs)comprise a large group of modular eukaryotic E3 ubiquitin ligases.Within this family,the CRL4 ligase(consisting of the Cullin4[CUL4]scaffold protein,the Rbxl RING finger domain protein,the DNA...Cullin-RING ligases(CRLs)comprise a large group of modular eukaryotic E3 ubiquitin ligases.Within this family,the CRL4 ligase(consisting of the Cullin4[CUL4]scaffold protein,the Rbxl RING finger domain protein,the DNA damage-binding protein 1[DDB1],and one of many DDBl-associated substrate receptor proteins)has been intensively studied in recent years due to its involvement in regulating various cellular processes,its role in cancer development and progression,and its subversion by viral accessory proteins.Initially discovered as a target for hijacking by the human immunodeficiency virus accessory protein r,the normal targets and function of the CRL4 substrate receptor protein DDBl-Cul4-associated factor 1(DCAF1;also known as VprBP)had remained elusive,but newer studies have begun to shed light on these questions.Here,we review recent progress in understanding the diverse physiological roles of this DCAF1 in supporting various general and cell type-specific cellular processes in its context with the CRL4 E3 ligase,as well as another HECT-type E3 ligase with which DCAF1 also associates,called EDD/UBR5.We also discuss emerging questions and areas of future study to uncover the dynamic roles of DCAF1 in normal physiology.展开更多
文摘目的:探讨双特异性酪氨酸磷酸化调节激酶2(dual-specificity tyrosine phosphorylation-regulated kinase2,DYRK2)在胰腺癌中的表达及其临床意义.方法:应用实时荧光定量PCR、Western blot及免疫组织化学技术检测40例胰腺癌及其癌旁正常组织标本中DYRK2mRNA和蛋白的表达量,并结合免疫组织化学结果及胰腺癌患者的临床病理资料进行统计学分析.结果:实时荧光定量PCR检测显示,DYRK2m R N A在胰腺癌及其癌旁组织中均有表达,但后者的表达水平明显高于前者(P<0.01);Western blot检测显示,在88.9%的癌组织中D Y R K2蛋白的表达量低于其对应的癌旁组织;免疫组织化学染色显示,DYRK2在胰腺癌组织中的阳性比例明显低于其癌旁组织(42.5%vs87.5%,X2=17.802,P<0.01),且DYRK2的表达与胰腺癌有无淋巴结转移相关(X2=6.32,P<0.05).结论:DYRK2在胰腺癌组织中表达下调,可能与胰腺癌的发生发展和淋巴结转移等恶性生物学行为相关.
基金Supported by the Open Research Fund Program of Key Laboratory of Marine Drugs(Ocean University of China),Grant of Ministry of Education to X.TAN,KLMD(OUC)200609the National Natural Science Foundation of China(No.30970423)
文摘Proteins of the DYRK(dual-specificity tyrosine-phosphorylation-regulated kinase) family are characterized by the presence of a conserved kinase domain and N-terminal DH box.DYRK2 is involved in regulating key developmental and cellular processes,such as neurogenesis,cell proliferation,cytokinesis,and cellular differentiation.Herein,we report that the ortholog of DYRK2 found in zebrafish shares about 70% identity with that of human,mouse,and chick.RT-PCR showed that DYRK2 is expressed maternally and zygotically.In-situ hybridization results show that DYRK2 is expressed in somite cells that will develop into muscles.Our results provide preliminary evidence for investigating the in-vivo function of DYRK2 in zebrafish muscle development.
文摘目的探讨微小RNA622(microRNA-622,miR-622)及双重特异性酪氨酸调节激酶2(DYRK2)在结肠癌组织及结肠细胞系SW1116、SW480中的表达情况并研究其对SW1116侵袭转移能力的影响。方法选取82例结肠癌及癌旁组织标本,培养结肠癌细胞系SW1116、SW480及正常结肠上皮细胞系NCM460细胞。Real time PCR检测组织及细胞中miR-622的表达,Real time PCR、免疫组织化学、Western blot检测DYRK2基因及蛋白的表达并行Pearson相关性分析。在SW1116中转染miR-622mimics上调miR-622表达,同时对照(NC)组转染阴性序列并验证,Real time PCR及Western blot进一步检测上调miR-622后SW1116中DYRK2基因及蛋白表达水平,同时用Transwell法检测SW1116细胞侵袭转移能力的变化。结果Real time PCR及Western blot结果显示,相比于癌旁组织和正常结肠上皮细胞系NCM460,结肠癌组织及结肠癌细胞SW1116中miR-622mRNA呈高表达而DYRK2mRNA及蛋白呈低表达,两者表达呈明显负相关(r=0.916,P<0.01)。转染miR-622 mimics后,Real time PCR及Western blot结果显示,相比于NC组,miR-622mimics组DYRK2mRNA及蛋白表达水平减低(P<0.01)。相应的,Transwell结果显示,相比于NC组,SW1116细胞转染miR-622mimics后侵袭转移能力明显增强(P<0.01)。结论结肠癌中miR-622呈高表达而DYRK2呈低表达,上调miR-622可负性调控DYRK2表达并促进SW1116细胞侵袭转移。
文摘Cullin-RING ligases(CRLs)comprise a large group of modular eukaryotic E3 ubiquitin ligases.Within this family,the CRL4 ligase(consisting of the Cullin4[CUL4]scaffold protein,the Rbxl RING finger domain protein,the DNA damage-binding protein 1[DDB1],and one of many DDBl-associated substrate receptor proteins)has been intensively studied in recent years due to its involvement in regulating various cellular processes,its role in cancer development and progression,and its subversion by viral accessory proteins.Initially discovered as a target for hijacking by the human immunodeficiency virus accessory protein r,the normal targets and function of the CRL4 substrate receptor protein DDBl-Cul4-associated factor 1(DCAF1;also known as VprBP)had remained elusive,but newer studies have begun to shed light on these questions.Here,we review recent progress in understanding the diverse physiological roles of this DCAF1 in supporting various general and cell type-specific cellular processes in its context with the CRL4 E3 ligase,as well as another HECT-type E3 ligase with which DCAF1 also associates,called EDD/UBR5.We also discuss emerging questions and areas of future study to uncover the dynamic roles of DCAF1 in normal physiology.
