We in vitro examined the existing prognoses of the dissociation constant, KD, between ТАТА- Binding Protein (TBP) and ТАТА box with single nucleotide polymorphism (SNP) associated with human diseases. Five SNP...We in vitro examined the existing prognoses of the dissociation constant, KD, between ТАТА- Binding Protein (TBP) and ТАТА box with single nucleotide polymorphism (SNP) associated with human diseases. Five SNPs of the genes for cytochrome P450 2A6 (associated with lung cancer), β-globin (associated with β-thalassemia), mannose binding lectin (associated with variable immunodeficiency), superoxide dismutase 1 (associated with amyotrophic lateral sclerosis) and triosephosphate isomerase (associated with anemia) fell within the range of –ln(KD;M/KD;WT) between –1.5 and –1 (here KD;WT and KD;M denote the normal ТАТА box and with SNP). The mea-surements using EMSA demonstrated that: 1) all the predictions stating that the affinity between ТВР and ТАТА boxes with SNPs would be reduced were correct;2) the departures of three predictions from the measurements fell within the confidence interval;3) all the predictions consistently underestimated actual mutational damage caused to ТАТА boxes with SNPs (a < 0.05;binomial law) and two of these predictions did so significantly (a < 0.05, Student’s t-test). This consistent underestimation seems to be associated with the damage to the context that modulates ТВP/ТАТА affinity, for example, the contact between the nucleosomal histone H3-Н4 dimer and the core promoter immediately near ТАТА boxes.展开更多
BACKGROUND Gastrointestinal stromal tumor(GIST)is a common neoplasm with high rates of recurrence and metastasis,and its therapeutic efficacy is still not ideal.There is an unmet need to find new molecular therapeutic...BACKGROUND Gastrointestinal stromal tumor(GIST)is a common neoplasm with high rates of recurrence and metastasis,and its therapeutic efficacy is still not ideal.There is an unmet need to find new molecular therapeutic targets for GIST.TATA-boxbinding protein-associated factor 15(TAF15)contributes to the progress of various tumors,while the role and molecular mechanism of TAF15 in GIST progression are still unknown.AIM To explore new molecular therapeutic targets for GIST and understand the biological role and underlying mechanisms of TAF15 in GIST progression.METHODS Proteomic analysis was performed to explore the differentially expressed proteins in GIST.Western blotting and immunohistochemical analysis were used to verify the expression level of TAF15 in GIST tissues and cell lines.Cell counting kit-8,colony formation,wound-healing and transwell assay were executed to detect the ability of TAF15 on cell proliferation,migration and invasion.A xenograft mouse model was applied to explore the role of TAF15 in the progression of GIST.Western blotting was used to detect the phosphorylation level and total level of RAF1,MEK and ERK1/2.RESULTS A total of 1669 proteins were identified as differentially expressed proteins with 762 upregulated and 907 downregulated in GIST.TAF15 was selected for the further study because of its important role in cell proliferation and migration.TAF15 was significantly over expressed in GIST tissues and cell lines.Overexpression of TAF15 was associated with larger tumor size and higher risk stage of GIST.TAF15 knockdown significantly inhibited the cell proliferation and migration of GIST in vitro and suppressed tumor growth in vivo.Moreover,the inhibition of TAF15 expression significantly decreased the phosphorylation level of RAF1,MEK and ERK1/2 in GIST cells and xenograft tissues,while the total RAF1,MEK and ERK1/2 had no significant change.CONCLUSION TAF15 is over expressed in GIST tissues and cell lines.Overexpression of TAF15 was associated with a poor prognosis of GIST patients.TAF1展开更多
In this editorial,the roles of tata-box-binding protein-associated factor 15(TAF15)in oncogenesis,tumor behavior,and as a therapeutic target in cancers in the context of gastrointestinal(GI)tumors are discussed concer...In this editorial,the roles of tata-box-binding protein-associated factor 15(TAF15)in oncogenesis,tumor behavior,and as a therapeutic target in cancers in the context of gastrointestinal(GI)tumors are discussed concerning the publication by Guo et al.TAF15 is a member of the FET protein family with a comprehensive range of cellular processes.Besides,evidence has shown that TAF15 is involved in many diseases,including cancers.TAF15 contributes to carcinogenesis and tumor behavior in many tumors.Besides,its relationship with the mitogen-activated protein kinases(MAPK)signaling pathway makes TAF15 a new target for therapy.Although,the fact that there is few studies investigating the expression of TAF15 constitutes a potential limitation in GI system,the association of TAF15 expression with aggressive tumor behavior and,similar to other organ tumors,the influence of TAF15 on the MAPK signaling pathway emphasize that this protein could serve as a new molecular biomarker to predict tumor behavior and target therapeutic intervention in GI cancers.In conclusion,more studies should be performed to better understand the prognostic and therapeutic role of TAF15 in GI tumors,especially in tumors resistant to therapy.展开更多
在口腔、食管和结直肠癌病灶中,TATA序列结合蛋白相关因子1(TATA-box binding protein associated factor 1 like,TAF1L)、stomatin家族蛋白1(stomatin-like protein 1,STOML1)和stomatin家族蛋白2(stomatin-like protein 2,STOML2)存...在口腔、食管和结直肠癌病灶中,TATA序列结合蛋白相关因子1(TATA-box binding protein associated factor 1 like,TAF1L)、stomatin家族蛋白1(stomatin-like protein 1,STOML1)和stomatin家族蛋白2(stomatin-like protein 2,STOML2)存在异常表达.为探究它们在消化系统癌变过程中的作用机理,利用6种消化道肿瘤(食道、胃、结肠、直肠、肝脏和胰腺)及癌旁组织的微陈列芯片,通过多重免疫组织化学染色,比对分析TAF1L、STOML1和STOML2这3种蛋白质在癌与癌旁组织的差异表达及与癌变的关联.结果发现,STOML2在食道、胃、结肠、直肠、肝脏和胰腺这6种消化系统癌组织中均呈显著性高表达(P<0.001),而同一家族成员STOML1则仅在食管癌和肝癌组织中表达明显增高(P<0.005).另外,除胰腺癌灶外,TAF1L在其余5种消化系统癌组织中也呈现高表达(P<0.005).同时,TAF1L、STOML1和STOML2这3种蛋白质均与上皮间充质转化的关键蛋白质MMP9有共定位现象.由此表明,3种蛋白质TAF1L、STOML1和STOML2在多种癌组织中可能具有广泛的促癌作用.由于3种蛋白质在多种癌组织的表达水平不同,说明它们各自存在着组织特异性,且具有不同的功能使命,需进一步研究TAF1L、STOML1和STOML2这3种蛋白质在消化系统恶性肿瘤发生发展过程中各自的分子病理学潜能,如能将它们打造成用于精准诊疗和预后判断的新型分子标志物,此研究结果将有重要的临床意义.展开更多
文摘We in vitro examined the existing prognoses of the dissociation constant, KD, between ТАТА- Binding Protein (TBP) and ТАТА box with single nucleotide polymorphism (SNP) associated with human diseases. Five SNPs of the genes for cytochrome P450 2A6 (associated with lung cancer), β-globin (associated with β-thalassemia), mannose binding lectin (associated with variable immunodeficiency), superoxide dismutase 1 (associated with amyotrophic lateral sclerosis) and triosephosphate isomerase (associated with anemia) fell within the range of –ln(KD;M/KD;WT) between –1.5 and –1 (here KD;WT and KD;M denote the normal ТАТА box and with SNP). The mea-surements using EMSA demonstrated that: 1) all the predictions stating that the affinity between ТВР and ТАТА boxes with SNPs would be reduced were correct;2) the departures of three predictions from the measurements fell within the confidence interval;3) all the predictions consistently underestimated actual mutational damage caused to ТАТА boxes with SNPs (a < 0.05;binomial law) and two of these predictions did so significantly (a < 0.05, Student’s t-test). This consistent underestimation seems to be associated with the damage to the context that modulates ТВP/ТАТА affinity, for example, the contact between the nucleosomal histone H3-Н4 dimer and the core promoter immediately near ТАТА boxes.
基金Supported by National Natural Science Foundation of China,No.81870453.
文摘BACKGROUND Gastrointestinal stromal tumor(GIST)is a common neoplasm with high rates of recurrence and metastasis,and its therapeutic efficacy is still not ideal.There is an unmet need to find new molecular therapeutic targets for GIST.TATA-boxbinding protein-associated factor 15(TAF15)contributes to the progress of various tumors,while the role and molecular mechanism of TAF15 in GIST progression are still unknown.AIM To explore new molecular therapeutic targets for GIST and understand the biological role and underlying mechanisms of TAF15 in GIST progression.METHODS Proteomic analysis was performed to explore the differentially expressed proteins in GIST.Western blotting and immunohistochemical analysis were used to verify the expression level of TAF15 in GIST tissues and cell lines.Cell counting kit-8,colony formation,wound-healing and transwell assay were executed to detect the ability of TAF15 on cell proliferation,migration and invasion.A xenograft mouse model was applied to explore the role of TAF15 in the progression of GIST.Western blotting was used to detect the phosphorylation level and total level of RAF1,MEK and ERK1/2.RESULTS A total of 1669 proteins were identified as differentially expressed proteins with 762 upregulated and 907 downregulated in GIST.TAF15 was selected for the further study because of its important role in cell proliferation and migration.TAF15 was significantly over expressed in GIST tissues and cell lines.Overexpression of TAF15 was associated with larger tumor size and higher risk stage of GIST.TAF15 knockdown significantly inhibited the cell proliferation and migration of GIST in vitro and suppressed tumor growth in vivo.Moreover,the inhibition of TAF15 expression significantly decreased the phosphorylation level of RAF1,MEK and ERK1/2 in GIST cells and xenograft tissues,while the total RAF1,MEK and ERK1/2 had no significant change.CONCLUSION TAF15 is over expressed in GIST tissues and cell lines.Overexpression of TAF15 was associated with a poor prognosis of GIST patients.TAF1
文摘In this editorial,the roles of tata-box-binding protein-associated factor 15(TAF15)in oncogenesis,tumor behavior,and as a therapeutic target in cancers in the context of gastrointestinal(GI)tumors are discussed concerning the publication by Guo et al.TAF15 is a member of the FET protein family with a comprehensive range of cellular processes.Besides,evidence has shown that TAF15 is involved in many diseases,including cancers.TAF15 contributes to carcinogenesis and tumor behavior in many tumors.Besides,its relationship with the mitogen-activated protein kinases(MAPK)signaling pathway makes TAF15 a new target for therapy.Although,the fact that there is few studies investigating the expression of TAF15 constitutes a potential limitation in GI system,the association of TAF15 expression with aggressive tumor behavior and,similar to other organ tumors,the influence of TAF15 on the MAPK signaling pathway emphasize that this protein could serve as a new molecular biomarker to predict tumor behavior and target therapeutic intervention in GI cancers.In conclusion,more studies should be performed to better understand the prognostic and therapeutic role of TAF15 in GI tumors,especially in tumors resistant to therapy.
文摘在口腔、食管和结直肠癌病灶中,TATA序列结合蛋白相关因子1(TATA-box binding protein associated factor 1 like,TAF1L)、stomatin家族蛋白1(stomatin-like protein 1,STOML1)和stomatin家族蛋白2(stomatin-like protein 2,STOML2)存在异常表达.为探究它们在消化系统癌变过程中的作用机理,利用6种消化道肿瘤(食道、胃、结肠、直肠、肝脏和胰腺)及癌旁组织的微陈列芯片,通过多重免疫组织化学染色,比对分析TAF1L、STOML1和STOML2这3种蛋白质在癌与癌旁组织的差异表达及与癌变的关联.结果发现,STOML2在食道、胃、结肠、直肠、肝脏和胰腺这6种消化系统癌组织中均呈显著性高表达(P<0.001),而同一家族成员STOML1则仅在食管癌和肝癌组织中表达明显增高(P<0.005).另外,除胰腺癌灶外,TAF1L在其余5种消化系统癌组织中也呈现高表达(P<0.005).同时,TAF1L、STOML1和STOML2这3种蛋白质均与上皮间充质转化的关键蛋白质MMP9有共定位现象.由此表明,3种蛋白质TAF1L、STOML1和STOML2在多种癌组织中可能具有广泛的促癌作用.由于3种蛋白质在多种癌组织的表达水平不同,说明它们各自存在着组织特异性,且具有不同的功能使命,需进一步研究TAF1L、STOML1和STOML2这3种蛋白质在消化系统恶性肿瘤发生发展过程中各自的分子病理学潜能,如能将它们打造成用于精准诊疗和预后判断的新型分子标志物,此研究结果将有重要的临床意义.
