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Differential expression and significance of 5-hydroxymethylcytosine modification in hepatitis B virus carriers and patients with liver cirrhosis and liver cancer
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作者 Yue-Cui Li Wei-Yue Hu +4 位作者 Cheng-Hang Li Li-Li Zhang Xiang-Wei Xu Jin Li Hong-Xia Luo 《World Journal of Gastrointestinal Surgery》 SCIE 2023年第3期346-361,共16页
BACKGROUND The relationship between hepatitis B surface antigen(HBsAg)-positive carrier status and liver cancer has been extensively studied.However,the epigenetic changes that occur during progression from HBsAg-posi... BACKGROUND The relationship between hepatitis B surface antigen(HBsAg)-positive carrier status and liver cancer has been extensively studied.However,the epigenetic changes that occur during progression from HBsAg-positive carrier status or cirrhosis to liver cancer are unknown.The epigenetic modification of DNA hydroxymethylation is critical in tumor development.Further,5-hydroxymethylcytosine(5hmC)is an important base for DNA demethylation and epigenetic regulation.It is also involved in the assembly of chromosomes and the regulation of gene expression.However,the mechanism of action of 5hmC in HBsAgpositive carriers or patients with cirrhosis who develop liver cancer has not been fully elucidated.AIM To investigate the possible epigenetic mechanism of HBsAg-positive carriers and hepatocellular carcinoma(HCC)progression from cirrhosis.METHODS Forty HBsAg-positive carriers,forty patients with liver cirrhosis,and forty patients with liver cancer admitted to the First People's Hospital of Yongkang between March 2020 and November 2021 were selected as participants.Free DNA was extracted using a cf-DNA kit.cfDNA was extracted by 5hmC DNA sequencing for principal component analysis,the expression profiles of the three groups of samples were detected,and the differentially expressed genes(DEGs)modified by hydroxymethylation were screened.Bioinformatic analysis was used to enrich DEGs,such as in biological pathways.RESULTS A total of 16455 hydroxymethylated genes were identified.Sequencing results showed that 32 genes had significant 5hmC modification differences between HBsAg carriers and liver cancer patients,of which 30 were upregulated and 2 downregulated in patients with HCC compared with HBsAg-positive carriers.Significant 5hmC modification differences between liver cirrhosis and liver cancer patients were identified in 20 genes,of which 17 were upregulated and 3 were downregulated in patients with HCC compared with those with cirrhosis.These genes may have potential loci that are undiscovered or unelucidated,which contribute to the development and progression of liver cancer.Analysis of gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes showed that the major signaling pathways involved in the differential genes were biliary secretion and insulin secretion.The analysis of protein interactions showed that the important genes in the protein-protein interaction network were phosphoenolpyruvate carboxykinase and solute carrier family 2.CONCLUSION The occurrence and development of liver cancer involves multiple genes and pathways,which may be potential targets for preventing hepatitis B carriers from developing liver cancer. 展开更多
关键词 Hepatitis B surface antigen 5-hydroxymethylcytosine Hepatocellular carcinoma Liver cancer DNA sequencing Differentially expressed genes
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Increased 5-hydroxymethylcytosine is a favorable prognostic factor of Helicobacter pylori-negative gastric cancer patients
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作者 Ying-Li Fu Yan-Hua Wu +4 位作者 Dong-Hui Cao Zhi-Fang Jia Ao Shen Jing Jiang Xue-Yuan Cao 《World Journal of Gastrointestinal Oncology》 SCIE 2022年第7期1295-1306,共12页
BACKGROUND Most gastric cancer(GC)patients are diagnosed at middle or late stage because the symptoms in early stage are obscure,which causes higher mortality rates of GC.Helicobacter pylori(H.pylori)was identified as... BACKGROUND Most gastric cancer(GC)patients are diagnosed at middle or late stage because the symptoms in early stage are obscure,which causes higher mortality rates of GC.Helicobacter pylori(H.pylori)was identified as a class I carcinogen and leads to aberrant DNA methylation/hydroxymethylation.5-hydroxymethylcytosine(5-hmC)plays complex roles in gene regulation of tumorigenesis and can be considered as an activating epigenetic mark of hydroxymethylation.AIM To explore the association between 5-hmC levels and the progression and prognosis of GC patients with or without H.pylori infection.METHODS A retrospective cohort study was conducted to estimate the predicted value of 5-hmC level in the progression and prognosis of GC patients with different H.pylori infection status.A total of 144 GC patients were recruited.RESULTS The levels of 5-hmC were significantly decreased in tumor tissues(0.076±0.048)compared with the matched control tissues(0.110±0.057,P=0.001).A high level of 5-hmC was an independent significant favorable predictor of overall survival in GC patients(hazard ratio=0.61,95% confidence interval:0.38-0.98,P=0.040),the H.pylori-negative GC subgroup(hazard ratio=0.30,95% confidence interval:0.13-0.68,P=0.004)and the GC patients with TNM stage Ⅰ or Ⅱ(hazard ratio=0.32,95% confidence interval:0.13-0.77,P=0.011).CONCLUSION Increased 5-hmC is a favorable prognostic factor in GC,especially for H.pylori-negative subgroups. 展开更多
关键词 5-hydroxymethylation 5-hydroxymethylcytosine Helicobacter pylori Gastric cancer PROGNOSIS
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TET2蛋白下调5hmC在膀胱癌细胞T739中低表达 被引量:1
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作者 谢梅茂 王忠军 +1 位作者 胡映秋 王晓荣 《中国医学创新》 CAS 2018年第8期36-39,共4页
目的:研究膀胱尿路上皮癌细胞中TET2蛋白及5hmC的表达量相关作用。方法:采用Real-time PCR检测正常尿路上皮细胞和膀胱尿路上皮癌细胞中TET2 mRNA的表达,并同时采用细胞免疫化学染色检测正常尿路上皮细胞和膀胱尿路上皮癌细胞中5m C及5... 目的:研究膀胱尿路上皮癌细胞中TET2蛋白及5hmC的表达量相关作用。方法:采用Real-time PCR检测正常尿路上皮细胞和膀胱尿路上皮癌细胞中TET2 mRNA的表达,并同时采用细胞免疫化学染色检测正常尿路上皮细胞和膀胱尿路上皮癌细胞中5m C及5hmC表达,了解TET与膀胱癌的作用关系,并探讨其可能的作用机制。结果:TET2 mRNA在正常膀胱细胞T24中的表达(1.400 00±0.057 74,n=3),显著高于膀胱癌T739细胞[(0.866 70±0.120 20,n=3),P=0.016 1];TET2蛋白在T739中表达(1.589 00±0.048 52,n=3)也明显低于T24[(1.310 00±0.049 33,n=3),P=0.015 7]。5-m C在两种细胞中的表达量比较差异无统计学意义(P=0.097 6);5-hm C的表达量T739细胞明显低于T24细胞[(1.840 00±0.055 68,n=3)VS(1.487 00±0.041 77,n=3),P=0.007 1)]。结论:TET2 mRNA和蛋白水平在膀胱肿瘤细胞中低表达,显著低于正常膀胱细胞;且TET2与5hmC低表达存在相关性。 展开更多
关键词 TET2 5hmc 膀胱癌
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TET酶及其中间产物5hmC研究进展
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作者 吴静妮 方小玲 +1 位作者 夏晓梦 章蒙蒙 《中南大学学报(医学版)》 CAS CSCD 北大核心 2019年第4期449-454,共6页
DNA甲基化是一种重要的表观遗传学修饰,在胚胎重编程、干细胞分化和肿瘤的发生中发挥调控作用。TET(ten-eleven translocation)酶为关键的去甲基化酶,可连续将5-甲基胞嘧啶(5-methylcytosine,5mC)氧化为5-羟甲基胞嘧啶(5-hydro-xymethyl... DNA甲基化是一种重要的表观遗传学修饰,在胚胎重编程、干细胞分化和肿瘤的发生中发挥调控作用。TET(ten-eleven translocation)酶为关键的去甲基化酶,可连续将5-甲基胞嘧啶(5-methylcytosine,5mC)氧化为5-羟甲基胞嘧啶(5-hydro-xymethylcytosine,5hmC)、5-甲酰胞嘧啶(5-formylcytosine,5fC)和5-羧基胞嘧啶(5-carboxylcytosine,5caC),这些碱基代表DNA的表观遗传修饰状态,同时调控DNA去甲基化的进程。研究TET蛋白如何调控DNA甲基化修饰和基因的表达有助于我们深入了解正常的生长发育和人类疾病的表观调控。 展开更多
关键词 表观遗传学 TET酶 5hmc DNA去甲基化
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Expression of TET and 5-HmC in Trophoblast Villi of Women with Normal Pregnancy and with Early Pregnancy Loss 被引量:1
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作者 Ai-hua WU Dong-yu YANG +4 位作者 Yu-dong LIU Xin CHEN Xu-long CHEN Shan LU Shi-ling CHEN 《Current Medical Science》 SCIE CAS 2018年第3期505-512,共8页
Increasing evidence suggests that epigenetic dysfunction may influence the stability of normal pregnancy. The ten-eleven translocation (TET) family and 5-hydroxymethylcytosine (5-hmC) were found to be linked with ... Increasing evidence suggests that epigenetic dysfunction may influence the stability of normal pregnancy. The ten-eleven translocation (TET) family and 5-hydroxymethylcytosine (5-hmC) were found to be linked with epigenetic reprogramming. The present study aimed to examine the expression of the TET family and 5-hmC in the villi of human embryos and compared their expression between normal pregnancy and early pregnancy loss (EPL). Embryonic villi were collected from normal pregnant women (control) experiencing medical abortion and from EPL patients at gestation ages of 6, 7 and 8 weeks. The mRNAs of TET family were analysed using quantitative polymerase chain reaction (qPCR), and TET proteins using Western blotting and immunohistochemical analysis. The MethylFlashTM Kit was used to quantify the absolute amount of 5-methylcytosine (5-mC) and 5-hmC. Our results showed that the expression of the TETs and 5-hmC in the normal villus decreased with increasing gestational age. Immunohistochemistry revealed that the TET proteins were expressed in the cytoplasm of trophoblasts and their expression was the highest in the 6-week tissue samples, which was consistent with the qPCR and Western blot results. The expression of TET1, TET2, and TET3 was lower in the villi in EPL group than in normal pregnancy group (P〈0.05 for all). It was concluded that the TET family and 5-hmC are critical in epigenetic reprogramming of human embryo. The findings also suggest that a deficiency of TETs in the villus might be associated with human EPL. 展开更多
关键词 early pregnancy loss VILLUS ten-eleven translocation 5-hydroxymethylcytosine 5-methylcytosine
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NJ-5HMC40五轴联动加工中心由宁江机床集团股份有限公司生产制造
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《机电新产品导报》 2003年第8期86-86,共1页
NJ-5HMC40是宁江为满足现代机械制造业的要求,最新构思设计的高速、高精机床。将高刚性的模块化结构及可靠性融为一体。确保了机床获得最佳的静态和动态刚性。使机床满足了五轴联动粗、精加工的要求。 机床广泛适用于叶片、叶轮、模具... NJ-5HMC40是宁江为满足现代机械制造业的要求,最新构思设计的高速、高精机床。将高刚性的模块化结构及可靠性融为一体。确保了机床获得最佳的静态和动态刚性。使机床满足了五轴联动粗、精加工的要求。 机床广泛适用于叶片、叶轮、模具工业。 展开更多
关键词 NJ-5hmc40五轴联动加工中心 宁江机床集团股份有限公司 机械制造业 技术参数
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5-Aza-CdR对德保黑猪手工克隆重构胚胎体外发育效果的影响
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作者 吕玲燕 陆杏蓉 +5 位作者 孙俊铭 陈宝剑 吴永绍 孙如玉 汪燕玲 崔奎青 《中国畜牧兽医》 CAS 北大核心 2018年第11期3144-3152,共9页
为了探讨5-氮杂-2′-脱氧胞苷(5-Aza-CdR)对德保黑猪手工克隆(HMC)重构胚胎体外发育效果的影响,本研究分别从供体细胞和重构胚入手,比较了5个不同处理浓度(0、5、10、20和40nmol/L)5-Aza-CdR处理HMC重构胚的体外发育效果,筛选最佳处理浓... 为了探讨5-氮杂-2′-脱氧胞苷(5-Aza-CdR)对德保黑猪手工克隆(HMC)重构胚胎体外发育效果的影响,本研究分别从供体细胞和重构胚入手,比较了5个不同处理浓度(0、5、10、20和40nmol/L)5-Aza-CdR处理HMC重构胚的体外发育效果,筛选最佳处理浓度;在最佳浓度下比较5个不同处理时间(0、24、48、72和96h)对HMC重构胚的体外发育效果,筛选最佳处理时间;用4个不同浓度(0、0.25、0.5和1μmol/L)5-Aza-CdR结合最佳浓度和最佳时间处理供体和重构胚,比较其体外发育潜能。结果显示,与空白对照组相比,5、10、20和40nmol/L5-Aza-CdR处理72h对重构胚卵裂率均无显著差异(P>0.05),20nmol/L 5-Aza-CdR处理能显著提高重构胚的囊胚率(P<0.05),10和20nmol/L 5-Aza-CdR处理均能显著提高囊胚细胞数(P<0.05),其中以20nmol/L 5-AzaCdR效果最佳;与空白对照组相比,利用20nmol/L 5-Aza-CdR处理HMC重构胚72h能显著提高重构胚的囊胚率和囊胚细胞数(P<0.05),其余处理时间对重构胚卵裂率、囊胚率和囊胚细胞数均无显著影响(P>0.05);在囊胚的最佳处理浓度(20nmol/L)和最佳处理时间(72h)下,结合供体的4个处理浓度(0、0.25、0.5和1μmol/L),同时处理重构胚和供体,各处理组HMC重构胚的发育潜能均有提高,但效果均不显著(P>0.05),其中0.25~0.5μmol/L 5-Aza-CdR处理效果较佳。综上表明,适宜浓度(0.25~0.5μmol/L)的DNA甲基化酶抑制剂5-AzaCdR处理供体细胞72h并结合20nmol/L 5-Aza-CdR处理重构胚72h均能有效提高德保黑猪HMC重构胚胎的体外发育潜能,该结果可为今后研究德保黑猪HMC胚胎DNA甲基化调控机制提供参考。 展开更多
关键词 5-氮杂-2′-脱氧胞苷(5-Aza-CdR) 德保黑猪 手工克隆(hmc) 发育效果
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TET1介导5-羟甲基胞嘧啶表达抑制突变型IDH1过表达胶质瘤细胞增殖、迁移和侵袭
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作者 雷梓 陈建功 +2 位作者 何颖 李睿 吴莹莹 《分子诊断与治疗杂志》 2021年第4期582-585,589,共5页
目的探讨TET1介导的5-羟甲基胞嘧啶(5hmC)表达对异柠檬酸脱氢酶1(IDH1)突变的U251胶质瘤细胞生物学行为的影响。方法构建R132H突变型IDH1(IDH1^(R132H))过表达载体,转染U251人胶质瘤细胞系,实时荧光定量PCR(RT-qPCR)及蛋白质免疫印迹(WB... 目的探讨TET1介导的5-羟甲基胞嘧啶(5hmC)表达对异柠檬酸脱氢酶1(IDH1)突变的U251胶质瘤细胞生物学行为的影响。方法构建R132H突变型IDH1(IDH1^(R132H))过表达载体,转染U251人胶质瘤细胞系,实时荧光定量PCR(RT-qPCR)及蛋白质免疫印迹(WB)检测IDH1^(R132H)及TET1表达水平,免疫荧光检测5hmC表达水平。IDH1^(R132H)过表达载体与TET过表达载体共转染U251细胞,RT-qPCR和WB检测TET1表达水平,利用CCK8实验检测肿瘤细胞增殖能力,划痕实验检测肿瘤细胞迁移能力,transwell小室实验检测肿瘤细胞侵袭能力,流式细胞实验检测肿瘤细胞周期及细胞凋亡。结果在IDH1^(R132H)过表达U251细胞中,TET1及5hmC表达水平降低,差异有统计学意义(P<0.05)。IDH1^(R132H)过表达U251细胞中过表达TET1后,5hmC水平升高,差异有统计学意义(P<0.05),同时抑制肿瘤细胞的增殖、迁移、侵袭能力,促进肿瘤细胞凋亡(P<0.05)。结论 TET1介导的5hmC表达能抑制IDH1^(R132H)过表达U251胶质瘤细胞的增殖、侵袭、迁移能力,促进肿瘤细胞凋亡。 展开更多
关键词 IDH突变 U251胶质瘤细胞 TET1 5hmc
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甲基化酶抑制剂5-Aza-CdR处理对德保猪手工克隆胚胎体外发育潜能的影响 被引量:3
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作者 陆杏蓉 孙俊铭 +5 位作者 李志鹏 李兰玉 谢炳坤 刘庆友 石德顺 崔奎青 《畜牧兽医学报》 CAS CSCD 北大核心 2014年第8期1274-1281,共8页
供体细胞的不完全重编程是动物克隆效率低的主要原因。本研究采用不同浓度(0.00(对照)、0.25、0.50和1.00μmol·L^(-1))的DNA甲基化转移酶抑制剂5-氮杂-2'-脱氧胞苷(5-Aza-2'-deoxycytidine,5-Aza-CdR)处理德保猪耳成纤维... 供体细胞的不完全重编程是动物克隆效率低的主要原因。本研究采用不同浓度(0.00(对照)、0.25、0.50和1.00μmol·L^(-1))的DNA甲基化转移酶抑制剂5-氮杂-2'-脱氧胞苷(5-Aza-2'-deoxycytidine,5-Aza-CdR)处理德保猪耳成纤维细胞,将处理后成纤维细胞作供体进行手工克隆。结果显示:各处理组细胞生长曲线均呈"S"型,其中0.25μmol·L^(-1)组细胞生长曲线与对照组最相近。随着5-Aza-CdR浓度增加,细胞均有不同程度的畸变、生长抑制甚至致死。0.00~0.50μmol·L^(-1)5-Aza-CdR处理对德保猪成纤维细胞不会显著改变其细胞染色体整倍性。5-Aza-CdR不同程度下调了德保猪耳成纤维细胞中Dnmtl、Tet1、Tet2和Tet3的相对表达,对Dnmt1、Tet1和Tet3表达量的下调呈剂量相关。以处理后成纤维细胞作供体,猪手工克隆重构胚体外发育的卵裂率(24、48 h)和桑椹胚率各组间差异不显著(P>0.05),其中0.25μmol·L^(-1)组和0.50μmol·L^(-1)组囊胚发育率显著高于1.00μmol·L^(-1)组(P<0.05),而与对照组差异不显著(P>0.05)。0.50μmol·L^(-1)组囊胚细胞数显著高于对照组和1.00μmol·L^(-1)组(P<0.05),而与0.25μmol·L^(-1)组之间差异不显著(P>0.05)。综上表明:高浓度5-Aza-CdR对德保猪成纤维细胞增殖和染色体具有副作用,低浓度(≤0.25μmol·L^(-1))的5-Aza-CdR可用于供体处理以降低克隆胚胎甲基化水平及提高手工克隆猪胚胎发育潜能。 展开更多
关键词 手工克隆 5-AZA-CDR 重编程
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DNA甲基化酶抑制剂5-Aza-CdR对多能基因及甲基化相关基因在徒手克隆胚胎中表达模式的影响 被引量:2
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作者 陆杏蓉 李志鹏 +5 位作者 孙俊铭 吕玲燕 许钟峯 刘庆友 石德顺 崔奎青 《中国畜牧兽医》 CAS 北大核心 2016年第9期2240-2248,共9页
本试验通过实时荧光定量PCR方法对多能基因Oct4和Nanog及DNA甲基化相关基因Dnmt1和Tets在徒手克隆(handmade cloning,HMC)胚胎中的表达模式进行初步研究,并探讨5-Aza-CdR处理重构胚对这些基因表达模式的影响。结果显示,Oct4、Nanog和Tet... 本试验通过实时荧光定量PCR方法对多能基因Oct4和Nanog及DNA甲基化相关基因Dnmt1和Tets在徒手克隆(handmade cloning,HMC)胚胎中的表达模式进行初步研究,并探讨5-Aza-CdR处理重构胚对这些基因表达模式的影响。结果显示,Oct4、Nanog和Tet3的表达在2细胞时期达到顶峰,Dnmt1和Tet2基因的表达随HMC胚胎发育而下降,而Tet1基因随HMC胚胎发育表达上升。使用5-Aza-CdR处理重构胚没有改变Oct4、Tet1和Tet3基因的表达模式,使Nanog基因在胚胎发育初期表达增加,Dnmt1和Tet2基因在胚胎发育初期表达降低。研究初步确立了Oct4、Nanog、Dnmt1和Tets基因在HMC胚胎的表达模式,5-Aza-CdR对重构胚的处理可对HMC胚胎的甲基化模式产生影响。 展开更多
关键词 徒手克隆 5-AZA-CDR 基因 表达模式
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5-羟甲基胞嘧啶在脑发育和神经系统疾病中的作用 被引量:1
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作者 蒋德伟 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2015年第6期549-555,共7页
大脑的发育和神经系统疾病的发生发展是极其复杂的过程,涉及多种因素.大量研究证实,表观遗传调控系统,如组蛋白甲基化、组蛋白乙酰化和DNA甲基化,是其中一类重要的调控因素.近年来研究发现,DNA去甲基化中间产物5-羟甲基胞嘧啶(5hm C)是... 大脑的发育和神经系统疾病的发生发展是极其复杂的过程,涉及多种因素.大量研究证实,表观遗传调控系统,如组蛋白甲基化、组蛋白乙酰化和DNA甲基化,是其中一类重要的调控因素.近年来研究发现,DNA去甲基化中间产物5-羟甲基胞嘧啶(5hm C)是一种新的表观遗传标记形式,且在神经元内呈现非常高的水平.这暗示5hm C可能在脑的生长发育以及中枢神经系统疾病的发生发展过程中有着重要的调控作用.本文综述了近年来该领域的重要研究进展,并且提出一些今后的研究展望. 展开更多
关键词 5-羟甲基胞嘧啶(5hmc) 脑发育 神经系统疾病 表观遗传调控
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Tet2 Regulates Osteoclast Differentiation by Interacting with Runx1 and Maintaining Genomic 5-Hydroxymethylcytosine(5hmC) 被引量:2
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作者 Yajing Chu Zhigang Zhao +15 位作者 David Wayne Sant Ganqian Zhu Sarah M. Greenblatt Lin Liu Jinhuan Wang Zeng Cao Jeanette Cheng Tho Shi Chen Xiaochen Liu Peng Zhang Jaroslaw P. Maciejewski Stephen Nimer Gaofeng Wang Weiping Yuan Feng-Chun Yang Mingjiang Xu 《Genomics, Proteomics & Bioinformatics》 SCIE CAS CSCD 2018年第3期172-186,共15页
As a dioxygenase. Ten-Eleven Translocation 2 (TET2) catalyzes subsequent steps of 5-methylcytosine (5mC) oxidation. TET2 plays a critical role in the self-renewal, proliferation, and differentiation of hei-natopoi... As a dioxygenase. Ten-Eleven Translocation 2 (TET2) catalyzes subsequent steps of 5-methylcytosine (5mC) oxidation. TET2 plays a critical role in the self-renewal, proliferation, and differentiation of hei-natopoietic stem cells, but its impact on mature hematopoietic cells is not well-characterized. Here we show that Tet2 plays an essential role in osteoclastogenesis. Dele- tion of Tet2 impairs the differentiation of osteoclast precursor cells (macrophages) and their matu- ration into bone-resorbing osteoclasts in vitro. Furthermore, Tet2 / mice exhibit mild osteopetrosis, accompanied by decreased number of osteoclasts in vivo. Tet2 loss in macrophages results in the altered expression of a set of genes implicated in osteoclast differentiation, such as Cehpa, Mafb, and Nfkbiz. Tet2 deletion also leads to a genome-wide alteration in the level of 5-hydroxymethylcytosine (ShmC) and altered expression of a specific subset of macrophage genes associated with osteoclast differentiation. Furthermore, Tet2 interacts with Runxl and negatively modulates its transcriptional activity. Our studies demonstrate a novel molecular mechanism controlling osteoclast differentiation and function by Tet2, that is, through interactions with Runxl and the maintenance of genomie 5hmC. Targeting Tet2 and its pathway could be a potential therapeutic strategy for the prevention and t,'eatment of abnormal bone mass caused by the deregulation of osteoclast activities. 展开更多
关键词 Tet2 5hmc MACROPHAGE OSTEOCLAST Runxl
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Towards precision medicine:advances in 5-hydroxymethylcytosine cancer biomarker discovery in liquid biopsy 被引量:9
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作者 Chang Zeng Emily Kunce Stroup +2 位作者 Zhou Zhang Brian C-HChiu Wei Zhang 《Cancer Communications》 SCIE 2019年第1期113-121,共9页
Robust and clinically convenient biomarkers for cancer diagnosis,early detection,and prognosis have great potential to improve patient survival and are the key to precision medicine.The advent of next-generation seque... Robust and clinically convenient biomarkers for cancer diagnosis,early detection,and prognosis have great potential to improve patient survival and are the key to precision medicine.The advent of next-generation sequencing technologies enables a more sensitive and comprehensive profiling of genetic and epigenetic information in tumor-derived materials.Researchers are now able to monitor the dynamics of tumorigenesis in new dimensions,such as using circulating cell-free DNA(cfDNA)and tumor DNA(ctDNA).Mutation-based assays in liquid biopsy cannot always provide consistent results across studies due partly to intra-and inter-tumoral heterogeneity as well as technical limitations.In contrast,epigenetic analysis of patient-derived cfDNA is a promising alternative,especially for early detection and disease surveillance,because epigenetic modifications are tissue-specific and reflect the dynamic process of cancer progression.Therefore,cfDNA-based epigenetic assays are emerging to be a highly sensitive,minimally invasive tool for cancer diagnosis and prognosis with great potential in future precise care of cancer patients.The major obstacle for applying epigenetic analysis of cfDNA,however,has been the lack of enabling techniques with high sensitivity and technical robustness.In this review,we summarized the advances in epigenome-wide profiling of 5-hydroxymethyl-cytosine(5hmC)in cfDNA,focusing on the detection approaches and potential role as biomarkers in different cancer types. 展开更多
关键词 Liquid biopsy Cell-free DNA EPIGENETICS Cancer biomarker 5-hydroxymethylcytosine
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Increased 5-hydroxymethylcytosine and Ten-eleven Translocation Protein Expression in Ultraviolet B-irradiated HaCaT Cells 被引量:2
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作者 Dan Wang Jin-Hua Huang +5 位作者 Qing-Hai Zeng Can Gu Shu Ding Jian-Yun Lu Jing Chen Sheng-Bo Yang 《Chinese Medical Journal》 SCIE CAS CSCD 2017年第5期594-599,共6页
Background: DNA hydroxymethylation refers to a chemical modification process in which 5-methylcytosine (5mC) is catalyzed to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (TET) family proteins. Rec... Background: DNA hydroxymethylation refers to a chemical modification process in which 5-methylcytosine (5mC) is catalyzed to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (TET) family proteins. Recent studies have revealed that aberrant TETs expression or 5hmC level may play important roles in the occurrence and development of various pathological and physiological processes including cancer and aging. This study aimed to explore the relation between aberrant DNA hydroxymethylation with skin photoaging and to investigate the levels of TETs, 5mC, and 5hmC expression 24 h after 40 mJ/cm^2 and 80 mJ/cm^2 doses of ultraviolet B (UVB) irradiation to HaCaT cells. Methods: To explore whether aberrant DNA hydroxymethylation is also related to skin photoaging, 40 mJ/cm^2 and 80 mJ/cm^2 doses of UVB were chosen to treat keratinocytes (HaCaT cells). After 24 h of UVB irradiation, 5mC and 5hmC levels were determined by immunohistochemistry (IHC) and immunofluorescence (IF), and at the same time, the expression levels of matrix metalloproteinase 1 (MMP-1) and TETs were assessed by reverse transcription-polymerase chain reaction or Western blot analysis. Results: After 40 mJ/cm^2 and 80 mJ/cm^2 doses of UVB exposure, both IHC and IF results showed that 5hmC levels increased significantly, while the 5mC levels did not exhibit significant changes in HaCaT cells, compared with HaCat cells without UVB exposure. Moreover, compared with HaCat cells without UVB exposure, the levels ofTET1, TET2, and TET3 mRNA and protein expression were significantly upregulated (mRNA: P = 0.0022 and 0.0043 for TET1; all P 〈 0.0001 for TET2; all P = 0.0006 for TET3; protein: P = 0.0012 and 0.0006 tbr TET 1 ; all P = 0.0022 for TET2; and all P = 0.0002 for TET3), and the levels of MMP- 1 mRNA expression increased dose dependently in 40 mJ/cm^2 and 80 mJ/cm^2 UVB-irradiated groups. Conclusion: UVB radiation could cause increased 5hmC and TET expression, which might become a novel biomarker in UVB-related skin aging. 展开更多
关键词 5-hydroxymethylcytosine 5-methylcytosine DNA Hydroxymethylation Ten-eleven Translocation Ultraviolet B
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Genome-wide 5-Hydroxymethylcytosine Profiling Analysis Identifies MAP7D1 as A Novel Regulator of Lymph Node Metastasis in Breast Cancer 被引量:1
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作者 Shuang-Ling Wu Xiaoyi Zhang +16 位作者 Mengqi Chang Changcai Huang Jun Qian Qing Li Fang Yuan Lihong Sun Xinmiao Yu Xinmiao Cui Jiayi Jiang Mengyao Cui Ye Liu Huan-Wen Wu Zhi-Yong Liang Xiaoyue Wang Yamei Niu Wei-Min Tong Feng Jin 《Genomics, Proteomics & Bioinformatics》 SCIE CAS CSCD 2021年第1期64-79,共16页
Although DNA 5-hydroxymethylcytosine(5 hmC)is recognized as an important epigenetic mark in cancer,its precise role in lymph node metastasis remains elusive.In this study,we investigated how 5 hmC associates with lymp... Although DNA 5-hydroxymethylcytosine(5 hmC)is recognized as an important epigenetic mark in cancer,its precise role in lymph node metastasis remains elusive.In this study,we investigated how 5 hmC associates with lymph node metastasis in breast cancer.Accompanying with high expression of TET1 and TET2 proteins,large numbers of genes in the metastasis-positive primary tumors exhibit higher 5 hmC levels than those in the metastasis-negative primary tumors.In contrast,the TET protein expression and DNA 5 hmC decrease significantly within the metastatic lesions in the lymph nodes compared to those in their matched primary tumors.Through genomewide analysis of 8 sets of primary tumors,we identified 100 high-confidence metastasis-associated5 hmC signatures,and it is found that increased levels of DNA 5 hmC and gene expression of MAP7 D1 associate with high risk of lymph node metastasis.Furthermore,we demonstrate that MAP7 D1,regulated by TET1,promotes tumor growth and metastasis.In conclusion,the dynamic5 hmC profiles during lymph node metastasis suggest a link between DNA 5 hmC and lymph node metastasis.Meanwhile,the role of MAP7 D1 in breast cancer progression suggests that the metastasis-associated 5 hmC signatures are potential biomarkers to predict the risk for lymph node metastasis,which may serve as diagnostic and therapeutic targets for metastatic breast cancer. 展开更多
关键词 5-hydroxymethylcytosine Breast cancer Lymph node metastasis MAP7D1 BIOMARKER
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Global changes of 5-hydroxymethylcytosine and 5-methylcytosine from normal to tumor tissues are associated with carcinogenesis and prognosis in colorectal cancer
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作者 Yi-ping TIAN Ai-fen LIN +6 位作者 Mei-fu GAN Hao WANG Dan YU Chong LAI Dan-dan ZHANG Yi-min ZHU Mao-de LAI 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2017年第9期747-756,共10页
Aberrant DNA methylation has raised widespread attention in tumorigenesis. In this study, we aimed to investigate the changes of global DNA methylation and hydroxymethylation from normal to tumor tissues in colorectal... Aberrant DNA methylation has raised widespread attention in tumorigenesis. In this study, we aimed to investigate the changes of global DNA methylation and hydroxymethylation from normal to tumor tissues in colorectal cancer(CRC) and their association with the prognosis. The levels of genomic 5-hydroxymethylcytosine(5hmC) and 5-methylcytosine(5mC) in cancerous tissues were significantly lower than those in corresponding adjacent normal tissues. The genomic levels of 5mC were significantly positively correlated with 5hmC in normal and cancerous tissues(all P<0.05). The ratio of 5mC in cancerous tissues to matched normal tissues(C/N-5mC) was also significantly positively correlated with the ratio of 5hmC in cancerous tissues to matched normal tissues(C/N-5hmC)(P=0.01). The 5mC levels and C/N-5mC ratios decreased with age(all P<0.05). Higher 5mC and 5hmC levels were found in rectal than in colon tissues(all P<0.05). High levels of 5mC in cancerous tissues and high C/N-5hmC ratios were each associated with lymph node metastasis(all P<0.05). Survival analysis indicated that the C/N-5mC ratio(P=0.04) is an independent protective factor for overall survival. The data showed that patients with a combination of high C/N-5hmC and low C/N-5mC ratios tended to have a worse prognosis(P<0.01). Our findings showed that the C/N-5mC ratio may be an independent prognostic factor for CRC outcome. Patients with both a high C/N-5hmC ratio and a low C/N-5mC ratio exhibited the worst survival, suggesting that 5mC and 5hmC can be used as critical markers in tumorigenesis and prognosis estimation. 展开更多
关键词 5-hydroxymethylcytosine(5hmc) 5-Methylcytosine(5mC) PROGNOSIS Colorectal cancer
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A simple and novel method for the quantitative detection of 5-hydroxymethylcytosine using carbon nanotube field- effect transistors
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作者 Fang Yuan Yanyan Deng +2 位作者 Wenyu Zhou Min Zhang Zigang Li 《Nano Research》 SCIE EI CAS CSCD 2016年第6期1701-1708,共8页
5-hydroxymethylcytosine (5-hmC) is an important epigenetic derivative of cytosine and quantitative detection of 5-hmC could be used as a reliable biomarker for a variety of human diseases. Current technologies used ... 5-hydroxymethylcytosine (5-hmC) is an important epigenetic derivative of cytosine and quantitative detection of 5-hmC could be used as a reliable biomarker for a variety of human diseases. Current technologies used in 5-hmC detection are complicated and time/cost inefficient. In this work, we report the first application of antibody-functionalized carbon nanotube field-effect transistors (CNT-FETs) in quantitative detection of 5-hmC from mouse tissues. This method achieves facile and ultra-sensitive 5-hmC detection based on electrical performance device and avoids complicated processing for DNA samples. The 5-hmC content percentages of normal mouse cerebrum, cerebellum, spleen, lung, liver, and heart samples presented in the genomic DNA were measured as 0.653, 0.573, 0.002, 0.020, 0.076, and 0.009, respectively, which is consistent with previous reports. This technology could be developed into fadle routine 5-hmC monitoring devices for clinic human disease diagnoses. 展开更多
关键词 5-hydroxymethylcytosine carbon nanotubefield-effect transistors BIOSENSOR
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A primer-initiated strand displacement amplification strategy for sensitive detection of 5-Hydroxymethylcytosine in genomic DNA
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作者 Yunda Li Yanfei Zhang +4 位作者 Zhenning Yu Yuzhi Xu Si-Yang Liu Zong Dai Xiaoyong Zou 《Chinese Chemical Letters》 SCIE CAS CSCD 2022年第8期3777-3781,共5页
5-Hydroxymethylcytosine(5 hmC),an intermediate product of DNA demethylation,is important for the regulation of gene expression during development and even tumorigenesis.The challenges associated with determination of ... 5-Hydroxymethylcytosine(5 hmC),an intermediate product of DNA demethylation,is important for the regulation of gene expression during development and even tumorigenesis.The challenges associated with determination of 5 hm C level include its extremely low abundance and high structural similarity with other cytosine derivatives,which resulted in sophisticated treatment with large amount of sample input.Herein,we developed a primer-initiated strand displacement amplification(PISDA)strategy to quantify the global 5 hm C in genomic DNA from mammalian tissues with high sensitivity/selectivity,low input and simple operation.This sensitive fluorescence method is based on 5 hmC-specific glucosylation,primer ligation and DNA amplification.After the primer was labeled on 5 hm C site,DNA polymerase and nicking enzyme will repeatedly act on each primer,causing a significant increase of fluorescence signal to magnify the minor difference of 5 hm C content from other cytosine derivatives.This method enables highly sensitive analysis of 5 hm C with a detection limit of 0.003%in DNA(13.6 fmol,S/N=3)from sample input of only 150 ng,which takes less than 15 min for determination.Further determination of 5 hmC in different tissues not only confirms the widespread presence of 5 hmC but also indicates its significant variation in different tissues and ages.Importantly,this PISDA strategy exhibits distinct advantages of bisulfite-free treatment,mild conditions and simple operation without the involvement of either expensive equipment or large amount of DNA sample.This method can be easily performed in almost all research and medical laboratories,and would provide a promising prospect to detect global 5 hmC in mammalian tissues. 展开更多
关键词 5-hydroxymethylcytosine DNA demethylation Fluorescence detection Strand displacement amplification Enzymatic labeling
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TET家族DNA羟化酶与5-hmC在肿瘤中的作用机制的研究进展 被引量:2
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作者 吴怡晨 凌志强 《中国细胞生物学学报》 CAS CSCD 北大核心 2013年第12期1806-1812,共7页
DNA甲基化失调引起基因表达异常是表观遗传学的一个显著特点。目前已知,由DNA甲基转移酶(DNA methyltransferases,DMNTs)催化DNA甲基化,其酶基因突变或表达异常引起DNA甲基化水平的改变。近期研究发现了一种DNA去甲基化酶—TET(Ten-Elev... DNA甲基化失调引起基因表达异常是表观遗传学的一个显著特点。目前已知,由DNA甲基转移酶(DNA methyltransferases,DMNTs)催化DNA甲基化,其酶基因突变或表达异常引起DNA甲基化水平的改变。近期研究发现了一种DNA去甲基化酶—TET(Ten-Eleven translocation)家族DNA羟化酶,能通过多种途径催化5-甲基胞嘧啶(5-methylcytosine,5-mC)去甲基化,从而调控DNA甲基化的平衡。5-羟甲基胞嘧啶(5-hydroxymethylcytosine,5-hmC)作为DNA去甲基化多重步骤中重要的中间产物,其水平在肿瘤的发生和发展时期发生显著变化。该文从TET家族蛋白展开,介绍TET蛋白的结构、功能及作用机制以及多种人类肿瘤中TET家族基因与5-hmC水平的相关性及其对肿瘤发生发展、诊断预后等临床意义的研究进展。 展开更多
关键词 TET家族DNA羟化酶 5-hmc 肿瘤 α-KG
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TET1和5hmC在上皮性卵巢癌组织中的表达及临床意义 被引量:1
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作者 赖允丽 张钦乐 +6 位作者 易升 陈璞琳 蒋丽 陈筠 许富本 覃再隆 马刚 《中国肿瘤临床与康复》 2018年第7期790-793,共4页
目的探讨TET1和5hm C在浆液上皮性卵巢癌组织中的表达及其与临床病理特点的关系。方法选取2016年02月至2017年02月间广西医科大学肿瘤医院收治的59例卵巢浆液上皮性组织样本,其中,浆液性囊腺癌组织30例,交界性浆液性囊腺瘤组织7例,浆液... 目的探讨TET1和5hm C在浆液上皮性卵巢癌组织中的表达及其与临床病理特点的关系。方法选取2016年02月至2017年02月间广西医科大学肿瘤医院收治的59例卵巢浆液上皮性组织样本,其中,浆液性囊腺癌组织30例,交界性浆液性囊腺瘤组织7例,浆液性囊腺瘤组织12例,并选取正常卵巢组织10例作为对照。采用免疫组化法观察TET1和5hm C蛋白的表达,采用Fisher和Spearman检验法进行相关性分析。结果与对照组相比,TET1和5hm C在囊腺癌组织中的表达升高最显著,差异均有统计学意义(均P<0.05)。在囊腺癌组织中,TET1在有淋巴结转移、病理学Ⅲ期和组织学高级别中的表达均高于无淋巴结转移、病理学Ⅰ~Ⅱ期和组织学低级别,差异均有统计学意义(均P<0.05)。结论 TET1和5hm C在浆液上皮性卵巢癌组织中高表达,TET1高表达与伴有淋巴结转移、病理学晚期和高组织学级别有关。 展开更多
关键词 TET1 5hmc 浆液上皮性卵巢肿瘤 临床病理特征
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