Objective This article aimed to review the biological characteristics of enhancer of zests homolog 2 （EZH2）, and the transcriptional repression mechanism of action of EZH2 in tumors, particularly in the progression ...Objective This article aimed to review the biological characteristics of enhancer of zests homolog 2 （EZH2）, and the transcriptional repression mechanism of action of EZH2 in tumors, particularly in the progression of lymphoma. Data sources The data cited in this review were mainly obtained from the articles listed in PubMed and HighWare that were published from March 2004 to April 2012. The search terms were ＂enhancer of zests homolog 2＂, ＂polycomb group＂, and ＂lymphoma＂. Study selection Articles regarding the mechanism of EZH2 in post-transcriptional modification, functions of polycomb group proteins, and the roles of EZH2 in lymphoma were selected. Results EZH2 acts as oncogene and involved in many kinds of tumors. Moreover, it plays an important role in tumorigenesis and lymphomagenesis by promoting the proliferation and aggressiveness of neoplastic cells, facilitating malignant tumor cell diffusion, and mediating transcriptional silencing. Conclusion EZH2 mediated transcriptional repression through its methyltransferase activity at the chromatin level has certain influence on lymphoma, and there might exist a therapeutic window for the development of new agents and identification of novel diagnostic markers based on EZH2.展开更多
Objectives:The eukaryotic initiation factor 4F(eIF4F)translation initiation complex inhibitors(eIF4Fi)were recently found to hyperactivate extracellular signal-regulated kinases 1/2(ERK1/2)signals,which contribute to ...Objectives:The eukaryotic initiation factor 4F(eIF4F)translation initiation complex inhibitors(eIF4Fi)were recently found to hyperactivate extracellular signal-regulated kinases 1/2(ERK1/2)signals,which contribute to acquired resistance to BRAF(B-Raf proto-oncogene,serine/threonine kinase)inhibitors in melanoma.This present study aims to elucidate how to overcome the resistance of the eIF4Fi in BRAFV600E mutant melanoma cells and explore the underlying mechanisms.Methods:Melanoma A375(vemurafenib[VEM]-sensitive)and A375R(VEM-resistant)cells were exposed to eIF4Fi RocA at varying doses and durations in vitro.We investigated the impact of RocA on the activity of ERK1/2,AKT serine/threonine kinase 1(AKT1),eIF4E,and enhancer of zeste homolog 2(EZH2).We then examined the impact of RocA on pro-apoptotic BH3-only proteins and proliferative proteins.We subsequently determined the effect of combined eIF4Fi,AKT1 inhibitor,EZH2 inhibitor or VEM on tumor growth in vitro and in vivo.Results:RocA inhibited proliferation and induced apoptosis in A375 cells,but inhibited proliferation in A375R cells.RocA rapidly reactivated ERK1/2 at 3 h and returned to baseline levels at 48 h.However,eIF4E and AKT1 activation began at 12 h and peaked at 48 h.ERK1/2 positively regulated EZH2 and EZH2-dependent expression of c-Fos and EGR1,while AKT1 negatively regulated c-Myc,c-Jun,and BMF,but positively regulated eIF4E.RocA downregulated ERK1/2(or EZH2,AKT1,and eIF4E)independent bcl-2 and Mcl-1 expression.AKT1i enhanced RocA-induced cell apoptosis,while EZH2i reduced RocA-induced cell proliferation.Combined CR-1-31-B,EZH2i,and AKT1i effectively overcame resistance to RocA and VEM resistance both in vitro and in vivo.Conclusion:The eIF4F complex inhibitor reactivates ERK1/2-EZH2 and AKT1 signaling pathways,resulting in resistance to both eIF4Fi and VEM.Combined administration of an eIF4Fi with EZH2 and AKT1 inhibitors effectively enhances sensitivity to both eIF4F complex and BRAF inhibitors.展开更多
Zeste增强子同源物2(enhancer of zeste homolog2,EZH2)的增强子是一种组蛋白H3赖氨酸27甲基转移酶,已被证明在多种肾脏疾病中发挥作用,本文通过检索、查阅近年来EZH2与肾脏疾病的相关文献资料,对EZH2在非肿瘤性肾脏疾病中的研究进展等...Zeste增强子同源物2(enhancer of zeste homolog2,EZH2)的增强子是一种组蛋白H3赖氨酸27甲基转移酶,已被证明在多种肾脏疾病中发挥作用,本文通过检索、查阅近年来EZH2与肾脏疾病的相关文献资料,对EZH2在非肿瘤性肾脏疾病中的研究进展等情况进行综述,以供大家研究参考。展开更多
目的探讨Zeste同源蛋白增强子2(EZH2)和性别决定区域Y盒蛋白6(SOX6)在糖尿病肾病患者血清中的水平及与病情严重程度和肾功能的相关性。方法选择2021年12月至2023年12月自贡市第一人民医院收治的120例糖尿病肾病患者作为回顾性研究的观...目的探讨Zeste同源蛋白增强子2(EZH2)和性别决定区域Y盒蛋白6(SOX6)在糖尿病肾病患者血清中的水平及与病情严重程度和肾功能的相关性。方法选择2021年12月至2023年12月自贡市第一人民医院收治的120例糖尿病肾病患者作为回顾性研究的观察对象(糖尿病肾病组),纳入同期同院收治的120例单纯糖尿病患者作为糖尿病组。收集患者的临床资料,采用酶联免疫吸附试验检测血清EZH2和SOX6水平,全自动生化分析仪测定患者24 h尿蛋白定量(24 h Upro)、血清肌酐(Scr)、胱抑素-C(Cys-C)、血尿素氮(BUN)、尿白蛋白/尿肌酐比值(UACR)水平。根据估算肾小球滤过率(e GFR)将糖尿病肾病患者分为轻度组[60~<90 mL/(min·1.73 m^(2)),n=47]、中度组[30~<60 mL/(min·1.73 m^(2)),n=40]、重度组[<30 m L/(min·1.73 m^(2)),n=33]。采用多因素logistic回归分析糖尿病肾病患者病情严重程度的影响因素,采用Spearman与Pearson相关性分析血清EZH2、SOX6水平与糖尿病肾病患者病情严重程度、肾功能指标的相关性。结果与糖尿病组比较,糖尿病肾病组患者血清EZH2[(26.52±5.25)pg/mL vs(4.13±0.62)pg/mL,t=46.396,P<0.01]、SOX6[(16.44±3.18)pg/mL vs(7.19±1.24)pg/mL,t=29.687,P<0.01]水平均较高。随着糖尿病肾病患者疾病严重程度的提高(轻度组→中度组→重度组),BUN、CysC、Scr、24 h Upro、EZH2、SOX6、UACR水平升高(P<0.05)。多因素logistic回归分析显示高水平的BUN、Cys-C、Scr、24 h Upro、EZH2、SOX6、UACR是糖尿病肾病患者病情严重程度的危险因素(P<0.05)。糖尿病肾病患者血清EZH2、SOX6水平分别与病情严重程度以及肾功能指标(BUN、Cys-C、Scr、24 h Upro)水平呈正相关(P<0.05)。结论糖尿病肾病患者血清EZH2、SOX6水平均升高,二者均与糖尿病肾病进展及肾功能减退相关。展开更多
This editorial examines a recent study that used radiomics based on computed tomography(CT)to predict the expression of the fibroblast-related gene enhancer of zeste homolog 2(EZH2)and its correlation with the surviva...This editorial examines a recent study that used radiomics based on computed tomography(CT)to predict the expression of the fibroblast-related gene enhancer of zeste homolog 2(EZH2)and its correlation with the survival of patients with hepatocellular carcinoma(HCC).By integrating radiomics with molecular analysis,the study presented a strategy for accurately predicting the expression of EZH2 from CT scans.The findings demonstrated a strong link between the radiomics model,EZH2 expression,and patient prognosis.This noninvasive approach provides valuable insights into the therapeutic management of HCC.展开更多
Objective:In recent decades,studies have underscored nuclear proteins and signaling pathways in prostate cancer(PCa)development.Key biomarkers like Enhancer of zeste homolog 2(EZH2)and Forkhead box M1(FOXM1)are expres...Objective:In recent decades,studies have underscored nuclear proteins and signaling pathways in prostate cancer(PCa)development.Key biomarkers like Enhancer of zeste homolog 2(EZH2)and Forkhead box M1(FOXM1)are expressed in both healthy and malignant prostate cells.This study aimed to demonstrate the relationship between pathological characteristics,survival,recurrence,and tissue expression of EZH2 and FOXM1 in high-risk PCa patients.Methods:PCa tissues were used in a retrospective analysis that spanned from September 2009 to August 2019.Inclusion criteria comprised pathological tumor stage(pT)3 patients with positive surgical margins or tumor proximity to inked margins within 5 mm.After case selection,tissue slides were stained for EZH2 and FOXM1 antibodies,and Allred scores were calculated.Patients or relatives of deceased patients were contacted for signed agreements and disease follow-ups.Results:The pT3b,ductal carcinoma component,and moderate EZH2 expression were associated with relapse(odds ratio[OR]6.21,95%confidence interval[CI]1.41-27.27,p=0.016;OR 7.29,95%CI 1.03-51.43,p=0.046;OR 5.96,95%CI 1.09-32.48,p=0.039;respectively).The unilateral and bilateral seminal vesicle invasion increased the likelihood of recurrence by 9.98 times and 5.36 times,and the risk of death by around 9.78 times and 10.79 times,respectively.The pT3b was linked to higher death likelihood(OR 7.16,95%CI 1.38-37.23,p=0.019),while moderate EZH2 expression did not show statistical significance(OR 4.54,95%CI 0.87-23.60,p=0.072,marginally).Pathological regional lymph node stage(pN)1 had significantly higher probability of mortality than pN unknown(3.9%vs.27%,p<0.001).PCa in the neck and apex of the prostate gland increased death risk tenfold.Conclusion:Sufficient immunoexpression of EZH2,ductal carcinoma component,and neoplastic proliferation in the seminal vesicles,apex and neck of the prostate gland correlates with elevated risks of recurrence and mortality.Clinicians should use these criteria for appropriate patient referrals,and a multicenter trial could provide accurate classifications.展开更多
BACKGROUND Stem cells from apical papilla(SCAPs)represent promising candidates for bone regenerative therapies due to their osteogenic potential.However,enhancing their differentiation capacity remains a critical chal...BACKGROUND Stem cells from apical papilla(SCAPs)represent promising candidates for bone regenerative therapies due to their osteogenic potential.However,enhancing their differentiation capacity remains a critical challenge.Enhancer of zeste homolog 2(EZH2),a histone H3 lysine 27 methyltransferase,regulates osteogenesis through epigenetic mechanisms,but its role in SCAPs remains unclear.We hypothesized that EZH2 modulates SCAP osteogenic differentiation via interaction with lysine demethylase 2B(KDM2B),offering a target for therapeutic intervention.AIM To investigate the functional role and molecular mechanism of EZH2 in SCAP osteogenic differentiation.METHODS SCAPs were isolated from healthy human third molars(n=6 donors).Osteogenic differentiation was assessed via Alizarin red staining and alkaline phosphatase assays.EZH2 overexpression/knockdown models were established using lentiviral vectors.Protein interactions were analyzed by co-immunoprecipitation,transcriptomic changes via microarray(Affymetrix platform),and chromatin binding by chromatin immunoprecipitation-quantitative polymerase chain reaction.In vivo bone formation was evaluated in immunodeficient mice(n=8/group)transplanted with SCAPs-hydroxyapatite scaffolds.Data were analyzed using Student’s t-test and ANOVA.RESULTS EZH2 overexpression increased osteogenic markers and mineralized nodule formation.In vivo,EZH2-overexpressing SCAPs generated 10%more bone/dentin-like tissue.Co-immunoprecipitation confirmed EZH2-KDM2B interaction,and peptide-mediated disruption of this binding enhanced osteogenesis.Transcriptome analysis identified 1648 differentially expressed genes(971 upregulated;677 downregulated),with pathway enrichment in Wnt/β-catenin signaling.CONCLUSION EZH2 promotes SCAP osteogenesis via antagonistic interaction with KDM2B,and targeted disruption of this axis offers a translatable strategy for bone regeneration.展开更多
文摘Objective This article aimed to review the biological characteristics of enhancer of zests homolog 2 （EZH2）, and the transcriptional repression mechanism of action of EZH2 in tumors, particularly in the progression of lymphoma. Data sources The data cited in this review were mainly obtained from the articles listed in PubMed and HighWare that were published from March 2004 to April 2012. The search terms were ＂enhancer of zests homolog 2＂, ＂polycomb group＂, and ＂lymphoma＂. Study selection Articles regarding the mechanism of EZH2 in post-transcriptional modification, functions of polycomb group proteins, and the roles of EZH2 in lymphoma were selected. Results EZH2 acts as oncogene and involved in many kinds of tumors. Moreover, it plays an important role in tumorigenesis and lymphomagenesis by promoting the proliferation and aggressiveness of neoplastic cells, facilitating malignant tumor cell diffusion, and mediating transcriptional silencing. Conclusion EZH2 mediated transcriptional repression through its methyltransferase activity at the chromatin level has certain influence on lymphoma, and there might exist a therapeutic window for the development of new agents and identification of novel diagnostic markers based on EZH2.
文摘Objectives:The eukaryotic initiation factor 4F(eIF4F)translation initiation complex inhibitors(eIF4Fi)were recently found to hyperactivate extracellular signal-regulated kinases 1/2(ERK1/2)signals,which contribute to acquired resistance to BRAF(B-Raf proto-oncogene,serine/threonine kinase)inhibitors in melanoma.This present study aims to elucidate how to overcome the resistance of the eIF4Fi in BRAFV600E mutant melanoma cells and explore the underlying mechanisms.Methods:Melanoma A375(vemurafenib[VEM]-sensitive)and A375R(VEM-resistant)cells were exposed to eIF4Fi RocA at varying doses and durations in vitro.We investigated the impact of RocA on the activity of ERK1/2,AKT serine/threonine kinase 1(AKT1),eIF4E,and enhancer of zeste homolog 2(EZH2).We then examined the impact of RocA on pro-apoptotic BH3-only proteins and proliferative proteins.We subsequently determined the effect of combined eIF4Fi,AKT1 inhibitor,EZH2 inhibitor or VEM on tumor growth in vitro and in vivo.Results:RocA inhibited proliferation and induced apoptosis in A375 cells,but inhibited proliferation in A375R cells.RocA rapidly reactivated ERK1/2 at 3 h and returned to baseline levels at 48 h.However,eIF4E and AKT1 activation began at 12 h and peaked at 48 h.ERK1/2 positively regulated EZH2 and EZH2-dependent expression of c-Fos and EGR1,while AKT1 negatively regulated c-Myc,c-Jun,and BMF,but positively regulated eIF4E.RocA downregulated ERK1/2(or EZH2,AKT1,and eIF4E)independent bcl-2 and Mcl-1 expression.AKT1i enhanced RocA-induced cell apoptosis,while EZH2i reduced RocA-induced cell proliferation.Combined CR-1-31-B,EZH2i,and AKT1i effectively overcame resistance to RocA and VEM resistance both in vitro and in vivo.Conclusion:The eIF4F complex inhibitor reactivates ERK1/2-EZH2 and AKT1 signaling pathways,resulting in resistance to both eIF4Fi and VEM.Combined administration of an eIF4Fi with EZH2 and AKT1 inhibitors effectively enhances sensitivity to both eIF4F complex and BRAF inhibitors.
文摘Zeste增强子同源物2(enhancer of zeste homolog2,EZH2)的增强子是一种组蛋白H3赖氨酸27甲基转移酶,已被证明在多种肾脏疾病中发挥作用,本文通过检索、查阅近年来EZH2与肾脏疾病的相关文献资料,对EZH2在非肿瘤性肾脏疾病中的研究进展等情况进行综述,以供大家研究参考。
文摘目的探讨Zeste同源蛋白增强子2(EZH2)和性别决定区域Y盒蛋白6(SOX6)在糖尿病肾病患者血清中的水平及与病情严重程度和肾功能的相关性。方法选择2021年12月至2023年12月自贡市第一人民医院收治的120例糖尿病肾病患者作为回顾性研究的观察对象(糖尿病肾病组),纳入同期同院收治的120例单纯糖尿病患者作为糖尿病组。收集患者的临床资料,采用酶联免疫吸附试验检测血清EZH2和SOX6水平,全自动生化分析仪测定患者24 h尿蛋白定量(24 h Upro)、血清肌酐(Scr)、胱抑素-C(Cys-C)、血尿素氮(BUN)、尿白蛋白/尿肌酐比值(UACR)水平。根据估算肾小球滤过率(e GFR)将糖尿病肾病患者分为轻度组[60~<90 mL/(min·1.73 m^(2)),n=47]、中度组[30~<60 mL/(min·1.73 m^(2)),n=40]、重度组[<30 m L/(min·1.73 m^(2)),n=33]。采用多因素logistic回归分析糖尿病肾病患者病情严重程度的影响因素,采用Spearman与Pearson相关性分析血清EZH2、SOX6水平与糖尿病肾病患者病情严重程度、肾功能指标的相关性。结果与糖尿病组比较,糖尿病肾病组患者血清EZH2[(26.52±5.25)pg/mL vs(4.13±0.62)pg/mL,t=46.396,P<0.01]、SOX6[(16.44±3.18)pg/mL vs(7.19±1.24)pg/mL,t=29.687,P<0.01]水平均较高。随着糖尿病肾病患者疾病严重程度的提高(轻度组→中度组→重度组),BUN、CysC、Scr、24 h Upro、EZH2、SOX6、UACR水平升高(P<0.05)。多因素logistic回归分析显示高水平的BUN、Cys-C、Scr、24 h Upro、EZH2、SOX6、UACR是糖尿病肾病患者病情严重程度的危险因素(P<0.05)。糖尿病肾病患者血清EZH2、SOX6水平分别与病情严重程度以及肾功能指标(BUN、Cys-C、Scr、24 h Upro)水平呈正相关(P<0.05)。结论糖尿病肾病患者血清EZH2、SOX6水平均升高,二者均与糖尿病肾病进展及肾功能减退相关。
文摘This editorial examines a recent study that used radiomics based on computed tomography(CT)to predict the expression of the fibroblast-related gene enhancer of zeste homolog 2(EZH2)and its correlation with the survival of patients with hepatocellular carcinoma(HCC).By integrating radiomics with molecular analysis,the study presented a strategy for accurately predicting the expression of EZH2 from CT scans.The findings demonstrated a strong link between the radiomics model,EZH2 expression,and patient prognosis.This noninvasive approach provides valuable insights into the therapeutic management of HCC.
文摘Objective:In recent decades,studies have underscored nuclear proteins and signaling pathways in prostate cancer(PCa)development.Key biomarkers like Enhancer of zeste homolog 2(EZH2)and Forkhead box M1(FOXM1)are expressed in both healthy and malignant prostate cells.This study aimed to demonstrate the relationship between pathological characteristics,survival,recurrence,and tissue expression of EZH2 and FOXM1 in high-risk PCa patients.Methods:PCa tissues were used in a retrospective analysis that spanned from September 2009 to August 2019.Inclusion criteria comprised pathological tumor stage(pT)3 patients with positive surgical margins or tumor proximity to inked margins within 5 mm.After case selection,tissue slides were stained for EZH2 and FOXM1 antibodies,and Allred scores were calculated.Patients or relatives of deceased patients were contacted for signed agreements and disease follow-ups.Results:The pT3b,ductal carcinoma component,and moderate EZH2 expression were associated with relapse(odds ratio[OR]6.21,95%confidence interval[CI]1.41-27.27,p=0.016;OR 7.29,95%CI 1.03-51.43,p=0.046;OR 5.96,95%CI 1.09-32.48,p=0.039;respectively).The unilateral and bilateral seminal vesicle invasion increased the likelihood of recurrence by 9.98 times and 5.36 times,and the risk of death by around 9.78 times and 10.79 times,respectively.The pT3b was linked to higher death likelihood(OR 7.16,95%CI 1.38-37.23,p=0.019),while moderate EZH2 expression did not show statistical significance(OR 4.54,95%CI 0.87-23.60,p=0.072,marginally).Pathological regional lymph node stage(pN)1 had significantly higher probability of mortality than pN unknown(3.9%vs.27%,p<0.001).PCa in the neck and apex of the prostate gland increased death risk tenfold.Conclusion:Sufficient immunoexpression of EZH2,ductal carcinoma component,and neoplastic proliferation in the seminal vesicles,apex and neck of the prostate gland correlates with elevated risks of recurrence and mortality.Clinicians should use these criteria for appropriate patient referrals,and a multicenter trial could provide accurate classifications.
基金Supported by National Key Research and Development Program,No.2022YFA1104401Beijing Natural Science Foundation,No.7222075+1 种基金CAMS Innovation Fund for Medical Sciences,No.2019RU020Innovation Research Team Project of Beijing Stomatological Hospital,No.CXTD202204.
文摘BACKGROUND Stem cells from apical papilla(SCAPs)represent promising candidates for bone regenerative therapies due to their osteogenic potential.However,enhancing their differentiation capacity remains a critical challenge.Enhancer of zeste homolog 2(EZH2),a histone H3 lysine 27 methyltransferase,regulates osteogenesis through epigenetic mechanisms,but its role in SCAPs remains unclear.We hypothesized that EZH2 modulates SCAP osteogenic differentiation via interaction with lysine demethylase 2B(KDM2B),offering a target for therapeutic intervention.AIM To investigate the functional role and molecular mechanism of EZH2 in SCAP osteogenic differentiation.METHODS SCAPs were isolated from healthy human third molars(n=6 donors).Osteogenic differentiation was assessed via Alizarin red staining and alkaline phosphatase assays.EZH2 overexpression/knockdown models were established using lentiviral vectors.Protein interactions were analyzed by co-immunoprecipitation,transcriptomic changes via microarray(Affymetrix platform),and chromatin binding by chromatin immunoprecipitation-quantitative polymerase chain reaction.In vivo bone formation was evaluated in immunodeficient mice(n=8/group)transplanted with SCAPs-hydroxyapatite scaffolds.Data were analyzed using Student’s t-test and ANOVA.RESULTS EZH2 overexpression increased osteogenic markers and mineralized nodule formation.In vivo,EZH2-overexpressing SCAPs generated 10%more bone/dentin-like tissue.Co-immunoprecipitation confirmed EZH2-KDM2B interaction,and peptide-mediated disruption of this binding enhanced osteogenesis.Transcriptome analysis identified 1648 differentially expressed genes(971 upregulated;677 downregulated),with pathway enrichment in Wnt/β-catenin signaling.CONCLUSION EZH2 promotes SCAP osteogenesis via antagonistic interaction with KDM2B,and targeted disruption of this axis offers a translatable strategy for bone regeneration.
