检索结果-南通市图书馆

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

引用

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 efficacy.We found that tet2 was poly-ubiquitinated by E3 ligase CUL7^(FBXW11) and degraded in EGFR-TKI resistant NSCLC ells.Genetic perturbationof tet2 rendered parental cells more tolerant to TKI treatment.tet2 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 resistance.Genetic or pharmacological inhibition of NF-kB attenuate the TKI resistance both in vitro and in vivo.Our 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 deficiency.Therefore,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

来源：

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

Association of DNA methylation/demethylation with the functional outcome of stroke in a hyperinflammatory state

引用

Neural Regeneration Research 2024年第10期19卷 2229-2239页

作者： Yubo Wang Ling Zhang Tianjie Lyu Lu Cui Shunying Zhao Xuechun Wang Meng Wang Yongjun Wang Zixiao Li Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina National Center for Healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering Research Center of Digital Healthcare for Neurological Diseases BeijingChina

Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke and has an important role in the functional out

关键词： DNA demethylation DNA methylation DNMT3A functional outcome hyperinflammatory state interleukin neuroinflammation stroke tet2

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

伴FLT3突变的急性髓系白血病患者共突变基因的临床特征及与预后的关系

引用

中国实验血液学杂志 2024年第4期 1032-1038页

作者：陈洋谢研研方玉洪鸣刘文洁周璇张巍师锦宁钱思轩南京医科大学附属江宁医院血液内科南京医科大学第一附属医院血液内科南京医科大学附属江宁医院输血科

目的:探讨伴有FLT3突变的初诊急性髓系白血病（AML）患者共突变基因的临床特征及其对患者预后生存的影响。方法:273例FLT3突变的AML患者纳入研究，收集患者的共突变基因资料，进一步对患者预后进行分析。FLT3等常见基因突变用PCR扩增产... 详细信息

目的:探讨伴有FLT3突变的初诊急性髓系白血病（AML）患者共突变基因的临床特征及其对患者预后生存的影响。方法:273例FLT3突变的AML患者纳入研究，收集患者的共突变基因资料，进一步对患者预后进行分析。FLT3等常见基因突变用PCR扩增产物直接测序和二代测序定量。结果:按FLT3突变的类型进行分组，分为FLT3ITD+、FLT3TKD+、FLT3ITD++TKD+和FLT3ITD-+TKD-组，其中tet2、GATA2、NRAS和ASXL1在4组间突变频率不同（均P2、C-kit在两组间突变频率不同（均Ptet2+AML患者的中位OS及无复发生存期（RFS）均短于FLT3++tet2-患者（均Ptet2共突变患者的中位OS和RFS较短。

关键词：急性髓系白血病 FLT3 共突变基因 tet2 预后

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

miR-660-5p靶向tet2促进乳腺癌的增殖、迁移和侵袭

引用

医学信息 2024年第1期37卷 95-102+114页

作者：张秀娟何莉莉田蜜李新复旦大学附属华东医院普外科荆门市人民医院甲乳外科荆门市公安局法医鉴定中心

目的研究miR-660-5p/tet2通过PI3K/AKT/mTOR信号通路调节乳腺癌细胞增殖、凋亡、迁移和侵袭的机制。方法收集2021年1月-2022年6月荆门市人民医院65例乳腺癌患者的乳腺癌组织和邻近正常组织样品，qPCR实验检测miR-660-5p在乳腺癌组织... 详细信息

目的研究miR-660-5p/tet2通过PI3K/AKT/mTOR信号通路调节乳腺癌细胞增殖、凋亡、迁移和侵袭的机制。方法收集2021年1月-2022年6月荆门市人民医院65例乳腺癌患者的乳腺癌组织和邻近正常组织样品，qPCR实验检测miR-660-5p在乳腺癌组织和细胞系中的表达水平，Kaplan-Meier生存分析和Log-rank检验分析miR-660-5p与患者临床病理特征的相关性；CCK8、流式细胞术和Transwell方法检测miR-660-5p对乳腺癌细胞增殖、凋亡、迁移和侵袭情况；双荧光素酶报告基因和蛋白质印迹实验明确miR-660-5p与tet2的关系；Western blot、CCK8和Transwell实验明确miR-660-5p通过靶向tet2调节乳腺癌的进程；Western blot实验检测miR-660-5p/tet2是否激活PI3K/AKT/mTOR信号通路；动物成瘤实验证明敲低miR-660-5p在乳腺癌中的作用。结果 miR-660-5p在乳腺癌组织中表达上调，且miR-660-5p的高表达与乳腺癌的淋巴结转移（P=0.003），晚期TNM分期（P=0.009）和血管浸润（P=0.018）密切相关；敲低miR-660-5p可抑制乳腺癌细胞增殖、迁移和侵袭，诱导乳腺癌细胞凋亡；tet2是miR-660-5p的直接靶标，干扰tet2可以部分逆转敲低miR-660-5p对乳腺癌细胞恶性潜能的抑制作用；miR-660-5p下调tet2并激活PI3K/AKT/mTOR信号通路；敲低miR-660-5p可抑制体内肿瘤生长。结论 miR-660-5p通过靶向tet2和PI3K/AKT/mTOR信号通路来促进乳腺癌的进程，可能是治疗乳腺癌的潜在靶标。

关键词：乳腺癌 miR-660-5p tet2 PI3K/AKT/mTOR信号通路

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

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

引用

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 expression.Ten-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 differentiation.Yet,the regulation of tet2 in the process of neuronal differentiation remains unknown.Here,the protein level of tet2 was reduced by the ubiquitin-proteasome pathway during NSC differentiation,in contrast to mRNA level.We 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 itself.The protein levels of GID complex subunits increased reciprocally with tet2 level upon NSC differentiation.The 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 NSC.tet2 level increased in the brain of the Wdr26^(+/-)mice.Our 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

来源：

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

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

引用

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

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

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

引用

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

来源：

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

The function and regulation of tet2 in innate immunity and inflammation

引用

Protein & Cell 2021年第3期12卷 165-173页

作者： Boyi Cong Qian Zhang Xuetao Cao Laboratory of Immunity and Inflammation College of Life SciencesNankai UniversityTianjin 300071China National Key Laboratory of Medical Immunology Institute of ImmunologyNavy Military Medical UniversityShanghai 200433China Department of Immunology Center for ImmunotherapyInstitute of Basic Medical SciencesChinese Academy of Medical SciencesBeijing 100005China

tet2,a member of ten-eleven translocation(tet)family as a-ketoglutarate-and Fe2+-dependent dioxygenase catalyzing the iterative oxidation of 5-methylcytosine(5mC),has been widely recognized to be an important regulator for normal hematopoiesis especially myelopoiesis.Mutation and dysregulation of tet2 contribute to the development of multiple hematological malignancies.Recent studies reveal that tet2 also plays an important role in innate immune homeostasis by promoting DNA demethylation or independent of its enzymatic activity.Here,we focus on the functions of tet2 in the initiation and resolution of inflammation through epigenetic regulation and signaling network.In addition,we highlight regulation of tet2 at various molecular levels as well as the correlated inflammatory diseases,which will provide the insight to intervene in the pathological process caused by tet2 dysregulation.

关键词： tet2 innate immune response DNA demethylation inflammatory resolution inflammatory diseases

来源：

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

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

引用

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

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

中南大学湘雅二医院:邓沱教授团队在肥胖和脂肪组织研究领域取得新进展

引用

中华医学信息导报 2024年第9期39卷 8-8页

作者：王丹丹赵晓华不详

本刊讯近日,中南大学湘雅二医院代谢内分泌科邓沱教授团队在Nature Communications发表了题为"A negative feedback loop between tet2 and leptin in adipocyte regulates body weight"的研究论文。

关键词：内分泌科脂肪组织 tet2

来源：

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

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：