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
Epigenetic regulation refers to alterations to the chromatin template that collectively establish differential patterns of gene transcription.Post-translational modifications of the histones play a key role in epigene...Epigenetic regulation refers to alterations to the chromatin template that collectively establish differential patterns of gene transcription.Post-translational modifications of the histones play a key role in epigenetic regulation of gene transcription.In this review,we provide an overview of recent studies on the role of histone modifications in carcinogenesis.Since tumour-selective ligands such as tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)are well-considered as promising anti-tumour therapies,we summarise strategies for improving TRAIL sensitivity by inhibiting aberrant histone modifications in cancers.In this perspective we also discuss new epigenetic drug targets for enhancing TRAIL-mediated apoptosis.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This research was partly funded by The Dutch Technology Foundation(STW)(No.11056)European Fund for Regional Development(KOP/EFRO)(No.068 and No.073).
文摘Epigenetic regulation refers to alterations to the chromatin template that collectively establish differential patterns of gene transcription.Post-translational modifications of the histones play a key role in epigenetic regulation of gene transcription.In this review,we provide an overview of recent studies on the role of histone modifications in carcinogenesis.Since tumour-selective ligands such as tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)are well-considered as promising anti-tumour therapies,we summarise strategies for improving TRAIL sensitivity by inhibiting aberrant histone modifications in cancers.In this perspective we also discuss new epigenetic drug targets for enhancing TRAIL-mediated apoptosis.
