When I was learning epigenetics 17 years ago at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins,this field was like a small spring bud growing in the windy storm of genetics/genomics.Now,epigenetics is ...When I was learning epigenetics 17 years ago at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins,this field was like a small spring bud growing in the windy storm of genetics/genomics.Now,epigenetics is booming like gold mining in the American West,and every cancer scientist intends to make a fortune from it.When epigenetics eventually becomes a mainstream,or even leading,research field in展开更多
Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic alterations.Recent studies revealed that abnormal gene expression induced by epigenetic changes,including aberrant pr...Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic alterations.Recent studies revealed that abnormal gene expression induced by epigenetic changes,including aberrant promoter methylation and histone modification,plays a critical role in human breast carcinogenesis.Silencing of tumor suppressor genes(TSGs) by promoter CpG methylation facilitates cells growth and survival advantages and further results in tumor initiation and progression,thus directly contributing to breast tumorigenesis.Usually,aberrant promoter methylation of TSGs,which can be reversed by pharmacological reagents,occurs at the early stage of tumorigenesis and therefore may serve as a potential tumor marker for early diagnosis and therapeutic targeting of breast cancer.In this review,we summarize the epigenetic changes of multiple TSGs involved in breast pathogenesis and their potential clinical applications as tumor markers for early detection and treatment of breast cancer.展开更多
Esophageal squamous cell carcinoma(ESCC) is a prevalent and fatal cancer in China and other Asian countries.Epigenetic silencing of key tumor suppressor genes(TSGs) is critical to ESCC initiation and progression.Recen...Esophageal squamous cell carcinoma(ESCC) is a prevalent and fatal cancer in China and other Asian countries.Epigenetic silencing of key tumor suppressor genes(TSGs) is critical to ESCC initiation and progression.Recently,many novel TSGs silenced by promoter methylation have been identified in ESCC,and these genes further serve as potential tumor markers for high-risk group stratification,early detection,and prognosis prediction.This review summarizes recent discoveries on aberrant promoter methylation of TSGs in ESCC,providing better understanding of the role of disrupted epigenetic regulation in tumorigenesis and insight into diagnostic and prognostic biomarkers for this malignancy.展开更多
Epstein-Barr virus(EBV)is a well-known human herpesvirus associated with virtually all nasopharyngeal carcinoma(NPC)and^10%of gastric cancer(GC)worldwide.Increasing evidence shows that acquired genetic and epigenetic ...Epstein-Barr virus(EBV)is a well-known human herpesvirus associated with virtually all nasopharyngeal carcinoma(NPC)and^10%of gastric cancer(GC)worldwide.Increasing evidence shows that acquired genetic and epigenetic alterations lead to the initiation and progression of NPC and GC.However,even deep whole exome sequencing studies showed a relatively low frequency of gene mutations in NPC and EBV-associated GC(EBVa GC),suggesting a predominant role of epigenetic abnormities,especially promoter Cp G methylation,in the pathogenesis of NPC and EBVa GC.High frequencies of promoter methylation of tumor suppressor genes(TSGs)have been frequently reported in NPC and EBVa GC,with several EBV-induced methylated TSGs identified.Further characterization of the epigenomes(genome-wide Cp G methylation profile—methylome)of NPC and EBVa GC shows that these EBV-associated tumors display a unique high Cp G methylation epigenotype with more extensive gene methylation accumulation,indicating that EBV acts as a direct epigenetic driver for these cancers.Mechanistically,oncogenic modulation of cellular Cp G methylation machinery,such as DNA methyltransferases(DNMTs),by EBV-encoded viral proteins accounts for the EBV-induced high Cp G methylation epigenotype in NPC and EBVa GC.Thus,uncovering the EBV-associated unique epigenotype of NPC and EBVa GC would provide new insight into the molecular pathogenesis of these unique EBVassociated tumors and further help to develop pharmacologic strategies targeting cellular methylation machinery in these malignancies.展开更多
Nasopharyngeal carcinoma(NPC) is a malignancy with remarkable ethnic and geographic distribution in southern China and Southeast Asia.Alternative to genetic changes,aberrant epigenetic events disrupt multiple genes in...Nasopharyngeal carcinoma(NPC) is a malignancy with remarkable ethnic and geographic distribution in southern China and Southeast Asia.Alternative to genetic changes,aberrant epigenetic events disrupt multiple genes involved in cell signaling pathways through DNA methylation of promoter CpG islands and/or histone modifications.These epigenetic alterations grant cell growth advantage and contribute to the initiation and progression of NPC.In this review,we summarize the epigenetic deregulation of cell signaling in NPC tumorigenesis and highlight the importance of identifying epigenetic cell signaling regulators in NPC research.Developing pharmacologic strategies to reverse the epigenetic-silencing of cell signaling regulators might thus be useful to NPC prevention and therapy.展开更多
Our previous studies found that Zinc-finger protein 382(ZNF382)played as a tumor suppressor gene in esophageal and gastric cancers,and a positive correlation between the high expression of ZNF382 and better outcome in...Our previous studies found that Zinc-finger protein 382(ZNF382)played as a tumor suppressor gene in esophageal and gastric cancers,and a positive correlation between the high expression of ZNF382 and better outcome in breast cancer patients.However,the biological roles and mechanisms of ZNF382 in breast cancer remains unclear.We detected ZNF382 expression by reverse-transcription PCR(RT-PCR)and real-time quantitative PCR(qRT-PCR)in breast cancer cells and tissues,and explored the impacts and mechanisms of ectopic ZNF382 expression in breast cancer cells in vitro and in vivo,respectively.Our results revealed that ZNF382 was significantly down-regulated in breast cancer tissues compared with adjacent non-cancer tissues.Restoration of ZNF382 expression in silenced breast cancer cells not only inhibited tumor cell colony formation,viability,migration and invasion,and epithelial-mesenchymal-transition(EMT),but also induced apoptosis and G0/G1 arrest.In conclusion,ZNF382 could induce G0/G1 cell cycle arrest through inhibiting CDC25A signaling,and,inhibit cell migration,invasion and EMT by antagonizing ZEB1 signaling in breast cancer cells.展开更多
A wide spectrum of metabolites(mainly,the three major nutrients and their derivatives)can be sensed by specific sensors,then trigger a series of signal transduction pathways and affect the expression levels of genes i...A wide spectrum of metabolites(mainly,the three major nutrients and their derivatives)can be sensed by specific sensors,then trigger a series of signal transduction pathways and affect the expression levels of genes in epigenetics,which is called metabolite sensing.Life body regulates metabolism,immunity,and inflammation by metabolite sensing,coordinating the pathophysiology of the host to achieve balance with the external environment.Metabolic reprogramming in cancers cause different phenotypic characteristics of cancer cell from normal cell,including cell proliferation,migration,invasion,angiogenesis,etc.Metabolic disorders in cancer cells further create a microenvironment including many kinds of oncometabolites that are conducive to the growth of cancer,thus forming a vicious circle.At the same time,exogenous metabolites can also affect the biological behavior of tumors.Here,we discuss the metabolite sensing mechanisms of the three major nutrients and their derivatives,as well as their abnormalities in the development of various cancers,and discuss the potential therapeutic targets based on metabolite-sensing signaling pathways to prevent the progression of cancer.展开更多
Epigenetics concerns non-DNA sequence dependent mechanisms through which cross-mitosis (and meiosis) transmission of committed gene expression pattern in high eukaryotes is achieved. The fact that cells with identic...Epigenetics concerns non-DNA sequence dependent mechanisms through which cross-mitosis (and meiosis) transmission of committed gene expression pattern in high eukaryotes is achieved. The fact that cells with identical genome can have plentiful phenotypic choices suggests a decisive role of epigenetic regulation in selective gene expression and therefore the biological activities at a cell type-specific manner in multi-cellular organisms. In addition to covalent chemical modifications of DNA and the core histones,展开更多
文摘When I was learning epigenetics 17 years ago at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins,this field was like a small spring bud growing in the windy storm of genetics/genomics.Now,epigenetics is booming like gold mining in the American West,and every cancer scientist intends to make a fortune from it.When epigenetics eventually becomes a mainstream,or even leading,research field in
基金supported by grants from the National Natural Science Foundation of China(NSFC)(No.#81072148,#81071634and#30928012)Natural Science Foundation of Chongqing(No.2010BB5101)Shenzhen Science Fund for Distinguished Young Scholars(No.JC201005270328A)
文摘Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic alterations.Recent studies revealed that abnormal gene expression induced by epigenetic changes,including aberrant promoter methylation and histone modification,plays a critical role in human breast carcinogenesis.Silencing of tumor suppressor genes(TSGs) by promoter CpG methylation facilitates cells growth and survival advantages and further results in tumor initiation and progression,thus directly contributing to breast tumorigenesis.Usually,aberrant promoter methylation of TSGs,which can be reversed by pharmacological reagents,occurs at the early stage of tumorigenesis and therefore may serve as a potential tumor marker for early diagnosis and therapeutic targeting of breast cancer.In this review,we summarize the epigenetic changes of multiple TSGs involved in breast pathogenesis and their potential clinical applications as tumor markers for early detection and treatment of breast cancer.
基金supported by NSFC Joint Research Fund for Hong Kong and Macao Young Scholars(No.30928012)National Natural Science Foundation of China(No.81071634,81172582,and 30801344)Shenzhen Science Fund for Distinguished Young Scholars(No.JC201005270328A)
文摘Esophageal squamous cell carcinoma(ESCC) is a prevalent and fatal cancer in China and other Asian countries.Epigenetic silencing of key tumor suppressor genes(TSGs) is critical to ESCC initiation and progression.Recently,many novel TSGs silenced by promoter methylation have been identified in ESCC,and these genes further serve as potential tumor markers for high-risk group stratification,early detection,and prognosis prediction.This review summarizes recent discoveries on aberrant promoter methylation of TSGs in ESCC,providing better understanding of the role of disrupted epigenetic regulation in tumorigenesis and insight into diagnostic and prognostic biomarkers for this malignancy.
基金Supported by grants from Health and Medical Research Fund(HMRF)(No.13120082)Hong Kong Research Grants Council(RGC)(No.474710 and T12-401/13R)+1 种基金National Natural Science Foundation of China(NSFC)(No.81372898 and 81172582)The Chinese University of Hong Kong
文摘Epstein-Barr virus(EBV)is a well-known human herpesvirus associated with virtually all nasopharyngeal carcinoma(NPC)and^10%of gastric cancer(GC)worldwide.Increasing evidence shows that acquired genetic and epigenetic alterations lead to the initiation and progression of NPC and GC.However,even deep whole exome sequencing studies showed a relatively low frequency of gene mutations in NPC and EBV-associated GC(EBVa GC),suggesting a predominant role of epigenetic abnormities,especially promoter Cp G methylation,in the pathogenesis of NPC and EBVa GC.High frequencies of promoter methylation of tumor suppressor genes(TSGs)have been frequently reported in NPC and EBVa GC,with several EBV-induced methylated TSGs identified.Further characterization of the epigenomes(genome-wide Cp G methylation profile—methylome)of NPC and EBVa GC shows that these EBV-associated tumors display a unique high Cp G methylation epigenotype with more extensive gene methylation accumulation,indicating that EBV acts as a direct epigenetic driver for these cancers.Mechanistically,oncogenic modulation of cellular Cp G methylation machinery,such as DNA methyltransferases(DNMTs),by EBV-encoded viral proteins accounts for the EBV-induced high Cp G methylation epigenotype in NPC and EBVa GC.Thus,uncovering the EBV-associated unique epigenotype of NPC and EBVa GC would provide new insight into the molecular pathogenesis of these unique EBVassociated tumors and further help to develop pharmacologic strategies targeting cellular methylation machinery in these malignancies.
基金supported by grants from Hong Kong RGC (GRF #473908 and #475009)National Natural Science Foundation of China (No. 81071634)
文摘Nasopharyngeal carcinoma(NPC) is a malignancy with remarkable ethnic and geographic distribution in southern China and Southeast Asia.Alternative to genetic changes,aberrant epigenetic events disrupt multiple genes involved in cell signaling pathways through DNA methylation of promoter CpG islands and/or histone modifications.These epigenetic alterations grant cell growth advantage and contribute to the initiation and progression of NPC.In this review,we summarize the epigenetic deregulation of cell signaling in NPC tumorigenesis and highlight the importance of identifying epigenetic cell signaling regulators in NPC research.Developing pharmacologic strategies to reverse the epigenetic-silencing of cell signaling regulators might thus be useful to NPC prevention and therapy.
基金supported by National Natural Science Foundation of China(No.81872380,81772869)Natural Science Foundation of Chongqing(No.2019ZX002,cstc2019jcjy-msxmX0861,cstc2020jcyj-bshX0025)+3 种基金Opening Foundation of Chongqing Key Laboratory of Molecular Oncology and Epigenetics(No.MOEL201702)Postdoctoral Science Fundation of China(No.2020M683262)National Key Research and Development Program of China(No.2017YFE0191700)HK RGC(No.GRF14115019).
文摘Our previous studies found that Zinc-finger protein 382(ZNF382)played as a tumor suppressor gene in esophageal and gastric cancers,and a positive correlation between the high expression of ZNF382 and better outcome in breast cancer patients.However,the biological roles and mechanisms of ZNF382 in breast cancer remains unclear.We detected ZNF382 expression by reverse-transcription PCR(RT-PCR)and real-time quantitative PCR(qRT-PCR)in breast cancer cells and tissues,and explored the impacts and mechanisms of ectopic ZNF382 expression in breast cancer cells in vitro and in vivo,respectively.Our results revealed that ZNF382 was significantly down-regulated in breast cancer tissues compared with adjacent non-cancer tissues.Restoration of ZNF382 expression in silenced breast cancer cells not only inhibited tumor cell colony formation,viability,migration and invasion,and epithelial-mesenchymal-transition(EMT),but also induced apoptosis and G0/G1 arrest.In conclusion,ZNF382 could induce G0/G1 cell cycle arrest through inhibiting CDC25A signaling,and,inhibit cell migration,invasion and EMT by antagonizing ZEB1 signaling in breast cancer cells.
基金supported by the National Natural Science Foundation of China[82072594(Y.T.),81874139,82073097(S.L.),81772496,82073136(D.X.)]Hunan Provincial Key Area R&D Programs[2019SK2253,2021SK2013,Y.T.]the Central South University Research Programme of Advanced Interdisciplinary Studies[2023QYJC030(Y.T.)].
文摘A wide spectrum of metabolites(mainly,the three major nutrients and their derivatives)can be sensed by specific sensors,then trigger a series of signal transduction pathways and affect the expression levels of genes in epigenetics,which is called metabolite sensing.Life body regulates metabolism,immunity,and inflammation by metabolite sensing,coordinating the pathophysiology of the host to achieve balance with the external environment.Metabolic reprogramming in cancers cause different phenotypic characteristics of cancer cell from normal cell,including cell proliferation,migration,invasion,angiogenesis,etc.Metabolic disorders in cancer cells further create a microenvironment including many kinds of oncometabolites that are conducive to the growth of cancer,thus forming a vicious circle.At the same time,exogenous metabolites can also affect the biological behavior of tumors.Here,we discuss the metabolite sensing mechanisms of the three major nutrients and their derivatives,as well as their abnormalities in the development of various cancers,and discuss the potential therapeutic targets based on metabolite-sensing signaling pathways to prevent the progression of cancer.
文摘Epigenetics concerns non-DNA sequence dependent mechanisms through which cross-mitosis (and meiosis) transmission of committed gene expression pattern in high eukaryotes is achieved. The fact that cells with identical genome can have plentiful phenotypic choices suggests a decisive role of epigenetic regulation in selective gene expression and therefore the biological activities at a cell type-specific manner in multi-cellular organisms. In addition to covalent chemical modifications of DNA and the core histones,