The reversible and precise temporal and spatial regulation of histone lysine methyltransferases(KMTs)is essential for epigenome homeostasis.The dysregulation of KMTs is associated with tumor initiation,metastasis,chem...The reversible and precise temporal and spatial regulation of histone lysine methyltransferases(KMTs)is essential for epigenome homeostasis.The dysregulation of KMTs is associated with tumor initiation,metastasis,chemoresistance,invasiveness,and the immune microenvironment.Therapeutically,their promising effects are being evaluated in diversified preclinical and clinical trials,demonstrating encouraging outcomes in multiple malignancies.In this review,we have updated recent understandings of KMTs'functions and the development of their targeted inhibitors.First,we provide an updated overview of the regulatory roles of several KMT activities in oncogenesis,tumor suppression,and immune regulation.In addition,we summarize the current targeting strategies in different cancer types and multiple ongoing clinical trials of combination therapies with KMT inhibitors.In summary,we endeavor to depict the regulation of KMT-mediated epigenetic landscape and provide potential epigenetic targets in the treatment of cancers.展开更多
Mesenchymal stem cells （MSCs） are characterized by their self-renewing capacity and differentiation potential into multiple tissues. Thus, management of the differentiation capacities of MSCs is important for MSC-ba...Mesenchymal stem cells （MSCs） are characterized by their self-renewing capacity and differentiation potential into multiple tissues. Thus, management of the differentiation capacities of MSCs is important for MSC-based regenerative medicine, such as craniofacial bone regeneration, and in new treatments for metabolic bone diseases, such as osteoporosis. In recent years, histone modification has been a growing topic in the field of MSC lineage specification, in which the Su（var）3-9, enhancer-of-zeste, trithorax （SET） domain-containing family and the Jumonji C （JmjC） domain-containing family represent the major histone lysine methyltransferases （KMTs） and histone lysine demethylases （KDMs）, respectively. In this review, we summarize the current understanding of the epigenetic mechanisms by which SET domain-containine KMTs and JmiC domain-containinlz KDMs balance the osteogenic and adipogenic differentiation of MSCs.展开更多
组蛋白甲基化转移酶SET和MYND结构域蛋白3(SET and MYND domain-containing protein 3,SMYD3)是催化组蛋白和非组蛋白底物甲基化的酶,在许多生物学环境中发挥关键作用,如肌肉发育和部分癌症的进展。本综述对SMYD3进行相关的基本介绍,并...组蛋白甲基化转移酶SET和MYND结构域蛋白3(SET and MYND domain-containing protein 3,SMYD3)是催化组蛋白和非组蛋白底物甲基化的酶,在许多生物学环境中发挥关键作用,如肌肉发育和部分癌症的进展。本综述对SMYD3进行相关的基本介绍,并探讨SMYD3在肺癌中的研究,旨在为SMYD3在肺癌中的进一步研究提供依据。展开更多
目的建立检测人血清中抗白色念珠菌H3K4甲基转移酶N末端肽段（N—terminal region of histone 3 lysine 4 methyhransferase，Setl-208p）IgG类抗体的ELISA方法，评估其在侵袭性念珠菌病（invasive candidiasis，IC）患者中的早期诊断...目的建立检测人血清中抗白色念珠菌H3K4甲基转移酶N末端肽段（N—terminal region of histone 3 lysine 4 methyhransferase，Setl-208p）IgG类抗体的ELISA方法，评估其在侵袭性念珠菌病（invasive candidiasis，IC）患者中的早期诊断价值。方法收集IC患者（105例）、定植患者（37例）、细菌感染患者（25例）、其他真菌感染患者（10例）以及健康体检者（200例）血清，用Setl-208p作为包被抗原，血清1：500稀释，以羊抗人IgG-HRP为二抗，测定人血清中相应的抗Setl-208p抗体水平，确定cut-off值并考查方法的敏感度、特异度和准确度。结果以重组Setl-208p抗原建立的ELISA法精密度良好，批内变异系数（coefficient of variation，CV）为5．5％，批间CV为10．4％。重组抗原对血清中相应抗体的阻断率为91．8％，根据ROC曲线，选择吸光度（absorbance，A）值0．40作为cut off值，对IC的诊断敏感度为79．2％，特异度为90％，且与细菌感染及其他真菌感染病人（如曲霉）无非特异交叉反应。此外，IC患者中抗Setl-208p抗体阳性率（76．1％，80／105）显著高于念珠菌定植者抗Setl-208p抗体阳性率（32．4％，12／37）（χ^2=22．9，P〈0．01）。结论建立了检测抗白念珠菌抗Setl-208p抗体的ELISA法，在IC早期诊断中具有潜在应用价值。展开更多
基金the Science and Technology Commission of Shanghai,China(Grant Nos.:20DZ2270800 and 19JC1410200)Innovative Research Team of High-Level Local Universities in Shanghai,China(Grant No.:SHSMU-ZDCX20210900)the National Natural Science Foundation of China(Grant No.:82073889).
文摘The reversible and precise temporal and spatial regulation of histone lysine methyltransferases(KMTs)is essential for epigenome homeostasis.The dysregulation of KMTs is associated with tumor initiation,metastasis,chemoresistance,invasiveness,and the immune microenvironment.Therapeutically,their promising effects are being evaluated in diversified preclinical and clinical trials,demonstrating encouraging outcomes in multiple malignancies.In this review,we have updated recent understandings of KMTs'functions and the development of their targeted inhibitors.First,we provide an updated overview of the regulatory roles of several KMT activities in oncogenesis,tumor suppression,and immune regulation.In addition,we summarize the current targeting strategies in different cancer types and multiple ongoing clinical trials of combination therapies with KMT inhibitors.In summary,we endeavor to depict the regulation of KMT-mediated epigenetic landscape and provide potential epigenetic targets in the treatment of cancers.
基金supported by the National Institute of Dental and Craniofacial Research grants, K08DE024603-02, DE019412, and DE01651a grant from 111 Project of MOE, Chinasupported by Open Fund of State Key Laboratory of Oral Diseases, Sichuan University
文摘Mesenchymal stem cells （MSCs） are characterized by their self-renewing capacity and differentiation potential into multiple tissues. Thus, management of the differentiation capacities of MSCs is important for MSC-based regenerative medicine, such as craniofacial bone regeneration, and in new treatments for metabolic bone diseases, such as osteoporosis. In recent years, histone modification has been a growing topic in the field of MSC lineage specification, in which the Su（var）3-9, enhancer-of-zeste, trithorax （SET） domain-containing family and the Jumonji C （JmjC） domain-containing family represent the major histone lysine methyltransferases （KMTs） and histone lysine demethylases （KDMs）, respectively. In this review, we summarize the current understanding of the epigenetic mechanisms by which SET domain-containine KMTs and JmiC domain-containinlz KDMs balance the osteogenic and adipogenic differentiation of MSCs.
文摘组蛋白甲基化转移酶SET和MYND结构域蛋白3(SET and MYND domain-containing protein 3,SMYD3)是催化组蛋白和非组蛋白底物甲基化的酶,在许多生物学环境中发挥关键作用,如肌肉发育和部分癌症的进展。本综述对SMYD3进行相关的基本介绍,并探讨SMYD3在肺癌中的研究,旨在为SMYD3在肺癌中的进一步研究提供依据。
文摘目的建立检测人血清中抗白色念珠菌H3K4甲基转移酶N末端肽段（N—terminal region of histone 3 lysine 4 methyhransferase，Setl-208p）IgG类抗体的ELISA方法，评估其在侵袭性念珠菌病（invasive candidiasis，IC）患者中的早期诊断价值。方法收集IC患者（105例）、定植患者（37例）、细菌感染患者（25例）、其他真菌感染患者（10例）以及健康体检者（200例）血清，用Setl-208p作为包被抗原，血清1：500稀释，以羊抗人IgG-HRP为二抗，测定人血清中相应的抗Setl-208p抗体水平，确定cut-off值并考查方法的敏感度、特异度和准确度。结果以重组Setl-208p抗原建立的ELISA法精密度良好，批内变异系数（coefficient of variation，CV）为5．5％，批间CV为10．4％。重组抗原对血清中相应抗体的阻断率为91．8％，根据ROC曲线，选择吸光度（absorbance，A）值0．40作为cut off值，对IC的诊断敏感度为79．2％，特异度为90％，且与细菌感染及其他真菌感染病人（如曲霉）无非特异交叉反应。此外，IC患者中抗Setl-208p抗体阳性率（76．1％，80／105）显著高于念珠菌定植者抗Setl-208p抗体阳性率（32．4％，12／37）（χ^2=22．9，P〈0．01）。结论建立了检测抗白念珠菌抗Setl-208p抗体的ELISA法，在IC早期诊断中具有潜在应用价值。
