检索结果-南通市图书馆

tet2 Regulates Osteoclast Differentiation by Interacting with Runx1 and Maintaining Genomic 5-Hydroxymethylcytosine(5hmC)

在线全文

学校读者我要写书评

暂无评论

Genomics, Proteomics & Bioinformatics 2018年第3期16卷 172-186页

作者： Yajing Chu Zhigang Zhao 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 State Key Laboratory of Experimental Hematology Institute of Hematology and Blood Diseases HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300020China Department of Hematology and Oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin 300060China Department of Oncology The Second Affiliated Hospital of Tianjin Medical UniversityTianjin 300211China Sylvester Comprehensive Cancer Center University of Miami Miller School of MedicineMiamiFL 33136USA Department of Human Genetics University of Miami Miller School of MedicineMiamiFL 33136USA Department of Biochemistry and Molecular Biology University of Miami Miller School of MedicineMiamiFL 33136USA Department of Medicine University of Miami Miller School of MedieineMiamiFL 33136USA Department of Translational Hematology and Oncology Research Taussig Cancer InstituteCleveland ClinicClevelandOH 44195USA

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.

关键词： tet2 5hmC Macrophage Osteoclast Runxl

tet methylcytosine dioxygenase 2(tet2)deficiency elicits EGFR-TKI(tyrosine kinase inhibitors)resistance in non-small cell lung cancer

在线全文

学校读者我要写书评

暂无评论

Signal Transduction and Targeted Therapy 2024年第4期9卷 1706-1720页

作者： Jian Zhang Kejia Zhao Wenjing Zhou Ran Kang Shiyou Wei Yueli Shu Cheng Yu Yin Ku Yonghong Mao Hao Luo Juqin Yang Jiandong Mei Qiang Pu Senyi Deng Zhengyu Zha Gang Yuan Shensi Shen Yaohui Chen Lunxu Liu Department of Thoracic Surgery and Institute of Thoracic Oncology West China Hospital of Sichuan UniversityChengdu 610097China Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer Sichuan UniversityChengdu 610097China Biobank of West China Hospital Sichuan UniversityChengdu 610041China

Despite epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKl)have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer(NSCLC),acquired resistance inevitably develops,limiting clinical *** found that tet2 was poly-ubiquitinated by E3 ligase CUL7^(FBXW11) and degraded in EGFR-TKI resistant NSCLC *** perturbationof tet2 rendered parental cells more tolerant to TKI ***2 was stabilized by MEK1 phosphorylation at Ser 1107,while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7^(FBXW11),Loss of tet2 resulted in the upregulation of TNF/NF-kB signaling that confers the EGFR-TKI *** or pharmacological inhibition of NF-kB attenuate the TKI resistance both in vitro and in *** findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating tet2,and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by tet2 ***,combined strategy exploiting EGFR-TKI and inhibitors of tet2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance.

关键词： tet2 TKI resistance

Sox2 induces glioblastoma cell sternness and tumor propagation by repressing tet2 and deregulating 5hmC and 5mC DNA modifications

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Signal Transduction and Targeted Therapy 2022年第3期7卷 790-801页

作者： Hernando Lopez-Bertoni Amanda Johnson Yuan Rui Bachchu Lai Sophie Sail Maureen Malloy Jonathan BCoulter Maria Lugo-Fagundo Sweta Shudir Harmon Khela Christopher Caputo Jordan J.Green John Laterra Hugo W.Moser Research Institute at Kennedy Krieger BaltimoreMDUSA Department of Neurology Johns Hopkins University School of MedicineBaltimoreMDUSA Department of Biomedical Engineering Institute for NanoBioTechnologyand the Translational Tissue Engineering CenterJohns Hopkins University School of MedicineBaltimoreMDUSA Bloomberg School of Public Health Department of Environmental Health and EngineeringThe Johns Hopkins University School of MedicineBaltimoreMDUSA The Department of Radiation Oncology and Molecular Radiation Sciences The Johns Hopkins University School of MedicineBaltimoreMDUSA Department of Ophthalmology Johns Hopkins University School of MedicineBaltimoreMDUSA Department of Oncology Johns Hopkins University School of MedicineBaltimoreMDUSA Departments of Materials Science&Engineering and Chemical&Biomolecular Engineering Johns Hopkins UniversityBaltimoreMDUSA Department of Neurosurgery Johns Hopkins University School of MedicineBaltimoreMDUSA Department of Neuroscience Johns Hopkins University School of MedicineBaltimoreMDUSA

DNA methylation is a reversible process catalyzed by the ten-eleven translocation(tet)family of enzymes(tet1,tet2,tet3)that convert 5-methylcytosine(5mC)to 5-hydroxymethylcytosine(5hmC).Altered patterns of 5hmC and 5m... 详细信息

关键词： tet2 5hmC convert

GID complex regulates the differentiation of neural stem cells by destabilizing tet2

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Frontiers of Medicine 2023年第6期17卷 1204-1218页

作者： Meiling Xia Rui Yan Wenjuan Wang Meng Zhang Zhigang Miao Bo Wan Xingshun Xu Department of Neurology The First Afiliated Hospital of Soochow UniversitySuzhou 215006China Institute of Neuroscience Soochow UniversitySuzhou 215006China Jiangsu Key Laboratory of Neuropsychiatric Diseases Soochow UniversitySuzhou 215123China

Brain development requires a delicate balance between self-renewal and differentiation in neural stem cells(NSC),which rely on the precise regulation of gene ***-eleven translocation 2(tet2)modulates gene expression by the hydroxymethylation of 5-methylcytosine in DNA as an important epigenetic factor and participates in the neuronal ***,the regulation of tet2 in the process of neuronal differentiation remains ***,the protein level of tet2 was reduced by the ubiquitin-proteasome pathway during NSC differentiation,in contrast to mRNA *** identified that tet2 physically interacts with the core subunits of the glucose-induced degradation-deficient(GID)ubiquitin ligase complex,an evolutionarily conserved ubiquitin ligase complex and is ubiquitinated by *** protein levels of GID complex subunits increased reciprocally with tet2 level upon NSC *** silencing of the core subunits of the GID complex,including WDR26 and ARMC8,attenuated the ubiquitination and degradation of tet2,increased the global 5-hydroxymethylcytosine levels,and promoted the differentiation of the ***2 level increased in the brain of the Wdr26^(+/-)*** results illustrated that the GID complex negatively regulates tet2 protein stability,further modulates NSC differentiation,and represents a novel regulatory mechanism involved in brain development.

关键词： tet2 GID complex neural stem cells differentiation of neurons

p53 promotes the expansion of regulatory T cells via DNMT3a-and tet2-mediated Foxp3 expression in sepsis

在线全文

学校读者我要写书评

暂无评论

Burns & Trauma 2023年第1期11卷 497-509页

作者： Hui Zhang Tiantian Wu Chao Ren Ning Dong Yao Wu Yongming Yao Translational Medicine Research Center Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General HospitalBeijingPeople’s Republic of China Department of Hepatobiliary Surgery Peking University International HospitalNo.1 Science Park RoadLife Science ParkChangping DistrictBeijing 100034People’s Republic of China Department of Respiratory and Critical Care Medicine Beijing Institute of Respiratory MedicineBeijing Chao-Yang HospitalCapital Medical UniversityNo.8 Worker’s Stadium South RoadChao-yang DistrictBeijingChina

Background:Immunosuppression is an important characteristic of sepsis and is closely related to poor *** T cells(Tregs)contribute to immune suppression by inhibiting effector T cell(Teff)proliferation and *** aimed to investigate the role of p53 in Treg expansion after ***:We constructed a sepsis model in wild-type(WT)and p53f/f/CD4-Cre+mice by cecal ligation and puncture(CLP)and evaluated the proportions of CD4+CD25+Foxp3+Tregs by flow *** expression levels of forkhead/winged helix transcription factor p3(Foxp3),DNA methyltransferase enzyme(DMNT)3a and ten-eleven translocation(tet)2 were examined using quantitative real-time PCR and Western blot ***-specific demethylation region(TSDR)methylation sites in cells were analyzed by bisulfite-sequencing ***,the direct binding of p53 to the Dnmt3a and tet2 promoters was illustrated using a luciferase *** suppressive ability of Tregs was indicated by enzyme-linked immunosorbent assay analysis of cytokine levels and the proliferation of cocultured ***,mortality rates after CLP were compared among WT and p53f/f/CD4-Cre+***:The proportion of CD4+CD25+Foxp3+Tregs was significantly reduced in p53f/f/CD4-Cre+mice compared to WT mice after *** enhanced expression of Foxp3 in WT mice was downregulated in the p53f/f/CD4-Cre+*** found decreased DMNT3a and increased tet2 levels after ***,the dysregulation of DNMT3a and tet2 was significantly reversed in p53f/f/CD4-Cre+*** underwent increased demethylation in p53f/f/CD4-Cre+*** activity indicated direct binding of p53 to the promoter regions of DNMT3a and tet2 to regulate their ***,Tregs from p53f/f/CD4-Cre+CLP mice exhibited limited suppressive ability,as indicated by the reduced production of transforming growth factor-βand interleukin 10(IL-10).In the coculture system,Teffs showed preserved production of IL-2,differentiation in

关键词： Sepsis Immunosuppression p53 Regulatory T cells Foxp3 DNMT3a tet2

Circular RNA circ ASK1 acts as a microRNA-22 sponge to attenuate intimal hyperplasia by regulating tet2

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

中国药理学与毒理学杂志 2019年第10期 802-803页

作者： XIA Luo-xing ZENG Zhi QIN Jing-hong LI Kang TANG Wai-ho Institute of Pediatrics Guangzhou Women and Children's Medical Centre Guangzhou Medical University

OBJECTIVE Circular RNA expression aberration has been identified in various human diseases. In this study, we investigated whether circ ASK1 could act as competing endogenous mi R-22 to regulate intimal hyperplasia. METHODS Quantitative polymerase chain reactions(q PCR) and fluorescent in situ hybridization(FISH) were conducted to detect circular ASK1(circ ASK1)expression in smooth muscle cells, mouse femoral artery and human arterial specimens. The q PCR assays, Western blotting assays, CCK-8 assays and Ed U(5-ethynyl-2′-deoxyuridine) incorporation assays were conducted to detect the functional roles of circ ASK1 in vascular smooth muscle cell function in vitro. Elastic Van Gienson and immunofluorescent assays were conducted to detect the role of circ ASK1 in intimal hyperplasia in vivo. Bioinformatics analysis, luciferase activity assays, RNA pulldown assays, and in vitro studies were conducted to reveal the mechanism of circ ASK1 on inhibiting intimal hyperplasia. RESULTS PDGF stimulation could reduce circ ASK1 expression in human(HASMC) and mouse aortic smooth muscle cells(MASMC). Moreover, circ ASK1 expression was significantly down-regulated in wireinjured femoral arteries and diseased arterial specimens were characterized by presence of SMC-rich atherosclerotic lesions. Up-regulation of circ ASK1 promoted differentiation and inhibited proliferation of mouse aortic smooth muscle cells(MASMC) in vitro. circ ASK1 overexpression in vivo alleviated intimal hyperplasia, as shown by promoting differentiation of smooth muscle *** ASK1 acted as an endogenous mi R-22 sponge to sequester and inhibit mi R-22 activity, which led to increased tet2 expression. Knockdown of mi R-22 mimicked the effect of circ ASK1 overexpression on MASMC phenotypes in vivo and in vitro. CONCLUSION Our results reveal an important role for a novel circ ASK1/mi R-22/tet2 axis in regulation of intimal hyperplasia. Overexpression of circ ASK1 promoted differentiation and inhibit proliferat

关键词： circular RNA circASK1 microRNA-22 vascular smooth muscle cell tet2 intimal hyperplasia

tet2合并DNMT3A突变及其他共存基因突变对急性髓系白血病患者预后的影响

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

中国肿瘤临床 2022年第21期49卷 1108-1114页

作者：孔繁聪齐凌黄文锋喻敏周玉兰李菲南昌大学第一附属医院血液病中心江西省血液病临床医学研究中心南昌市330006

目的:探究tet2合并DNMT3A突变及其他共存基因突变对成人非M3型急性髓系白血病(acute myeloid leukemia,AML)患者预后的影响。方法:回顾性分析2018年1月至2021年9月于南昌大学第一附属医院确诊的初治且行血液肿瘤相关突变基因外显子二代... 详细信息

目的:探究tet2合并DNMT3A突变及其他共存基因突变对成人非M3型急性髓系白血病(acute myeloid leukemia,AML)患者预后的影响。方法:回顾性分析2018年1月至2021年9月于南昌大学第一附属医院确诊的初治且行血液肿瘤相关突变基因外显子二代测序检测的512例成人AML(非M3型)患者的临床资料,分析患者的临床特征、疗效及生存情况。结果:本研究共纳入110例AML患者,tet2突变组64例,DNMT3A单突变组46例。男性50例(45.5%),中位年龄54(15~79)岁。tet2基因突变频率为12.5%(64/512),98.4%(63/64)患者突变基因数≥2个,每例患者平均合并5.2个突变基因。NPM1(43.8%)、DNMT3A(42.2%)、FLT3-ITD/TKD(40.6%)、CEBPA(26.6%)、TTN(20.3%)为tet2突变常见的共存突变基因。tet2合并DNMT3A突变患者初次诱导完全缓解(complete response,CR)率为46.2%,略低于tet2单突变患者的76.9%(P=0.077),与DNMT3A单突变患者无显著性差异(P=0.952)。tet2合并DNMT3A突变患者的中位总生存(median overall survival,mOS)时间为9.5个月,明显低于tet2单突变患者(P=0.002),而与DNMT3A单突变患者无显著性差异(P=0.414)。三者的中位无复发生存(median relapse-free survival,mRFS)时间无显著性差异(P>0.05)。在tet2突变背景下,合并K/NRAS突变患者的CR率为28.6%,明显低于无K/NRAS突变患者的75.0%(P=0.030),合并FLT3-ITD突变患者的mOS明显短于无FLT3-ITD突变患者(P=0.030)。多因素分析显示年龄≥60岁、合并FLT3-ITD突变、初次诱导未达CR是影响tet2突变AML患者总生存时间(overall survival,OS)的独立危险因素,DNMT3A突变不影响tet2突变患者OS。结论:tet2突变是AML患者常见突变,且常合并共存基因突变。共存基因突变与tet2突变共同影响AML患者预后。基于二代测序的基因突变检测对指导AML精确分层及精准治疗具有重要意义。

关键词：急性髓系白血病 tet2 DNMT3A 共存基因突变预后

在线全文

学校读者我要写书评

暂无评论

tet2基因在血液系统疾病中的研究进展

中国实验血液学杂志 2014年第3期22卷 836-841页

作者：李爽王小钦复旦大学附属华山医院血液科上海200040

几年前发现了tet基因家族。最近研究表明,tet2(tet基因家族成员2)在DNA去甲基化修饰、表观遗传调控及骨髓造血中扮演着重要角色,在一系列骨髓恶性肿瘤中,包括骨髓增殖性肿瘤、骨髓增生异常综合征及白血病也检测到tet2突变,揭示了tet2肿... 详细信息

几年前发现了tet基因家族。最近研究表明,tet2(tet基因家族成员2)在DNA去甲基化修饰、表观遗传调控及骨髓造血中扮演着重要角色,在一系列骨髓恶性肿瘤中,包括骨髓增殖性肿瘤、骨髓增生异常综合征及白血病也检测到tet2突变,揭示了tet2肿瘤抑制基因的作用。本文对tet2基因在血液系统疾病中的研究进展作一综述,包括tet基因的表观遗传调控功能,tet2基因与骨髓造血调控和tet2基因与血液系统疾病等问题。

关键词： tet2 表观遗传学骨髓增殖性肿瘤骨髓增生异常综合征白血病

在线全文

学校读者我要写书评

暂无评论

tet2基因突变在髓系肿瘤中的研究进展

中国医学科学院学报 2016年第5期38卷 583-588页

作者：李荣许明江杨逢春周圆中国医学科学院北京协和医学院血液学研究所&血液病医院实验血液学国家重点实验室天津300020

tet2为tet家族成员之一,是一个与造血系统发育密切相关的肿瘤抑制基因。近年研究发现,tet2通过将DNA上的5-甲基胞嘧啶(5-mc)氧化为5-羟甲基胞嘧啶(5-hmc),参与DNA的去甲基化过程。体细胞中tet2基因异常会导致骨髓生成异常及恶性髓系疾... 详细信息

tet2为tet家族成员之一,是一个与造血系统发育密切相关的肿瘤抑制基因。近年研究发现,tet2通过将DNA上的5-甲基胞嘧啶(5-mc)氧化为5-羟甲基胞嘧啶(5-hmc),参与DNA的去甲基化过程。体细胞中tet2基因异常会导致骨髓生成异常及恶性髓系疾病的发生。本文将就tet2的结构与功能,tet2基因突变与不同类型髓系肿瘤的关系进行综述。

关键词： tet2 突变髓系肿瘤