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P300/CBP-associated factor(PCAF)-mediated acetylation of Fascin at lysine 471 inhibits its actin-bundling activity and tumor metastasis in esophageal cancer

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Cancer Communications 2021年第12期41卷 1398-1416页

作者： Yin-wei Cheng Fa-Min Zeng Da-Jia Li Shao-Hong wang jian-Zhong He Zhen-Chang Guo Ping-Juan Nie Zhi-Yong Wu Wen-Qi Shi Bing Wen Xiu-E Xu Lian-Di Liao Zhi-mao Li jian-Yi Wu Jun Zhan Hong-Quan zhang Zhi-Jie Chang Kai zhang Li-Yan Xu En-Min Li The Key laboratory of molecular biology for High Cancer Incidence Coastal Chaoshan Area Department of Biochemistry and Molecular BiologyShantou University Medical CollegeShantouGuangdong 515041P.R.China institute of Basic Medical Science Cancer Research CenterShantou University Medical CollegeShantouGuangdong 515041P.R.China Shantou Central Hospital Affiliated Shantou Hospital of Sun Yat-sen UniversityShantouGuangdong 515041P.R.China Guangdong Provincial Key laboratory of Infectious Diseases and molecular Immunopathology Institute of Oncologic PathologyShantou University Medical CollegeShantouGuangdong 515041P.R.China Tianjin Key laboratory of Medical Epigenetics Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesTianjin Medical UniversityTianjin 300070P.R.China State Key laboratory of Natural and Biomimetic Drugs Peking University Health Science CenterBeijing 100191P.R.China School of Medicine Tsinghua UniversityBeijing 100084P.R.China

Background:Fascin is crucial for cancer cell filopodium formation and tumor metastasis,and is functionally regulated by post-translational ***,whether and how Fascin is regulated by acetylation remains *** study explored the regulation of Fascin acetylation and its corresponding roles in filopodium formation and tumor ***:Immunoprecipitation and glutathione-S-transferase pull-down assays were performed to examine the interaction between Fascin and acetyltransferase P300/CBP-associated factor(PCAF),and immunofluorescence was used to investigate their *** in vitro acetylation assay was performed to identify Fascin acetylation sites by using mass spectrometry.A specific antibody against acetylated Fascin was generated and used to detect the PCAF-mediated Fascin acetylation in esophageal squamous cell carcinoma(ESCC)cells using Western blotting by overexpressing and knocking down PCAF *** in vitro cell migration assay was performed,and a xenograft model was established to study in vivo tumor ***-cell imaging and fluorescence recovery after photobleaching were used to evaluate the function and dynamics of acetylated Fascin in filopodium *** clinical significance of acetylated Fascin and PCAF in ESCC was evaluated using ***:Fascin directly interacted and colocalized with PCAF in the cytoplasm and was acetylated at lysine 471(K471)by *** the specific antiAcK471-Fascin antibody,Fascin was found to be acetylated in ESCC cells,and the acetylation level was consequently increased after PCAF overexpression and decreased after PCAF ***,Fascin-K471 acetylation markedly suppressed in vitro ESCC cell migration and in vivo tumor metastasis,whereas Fascin-K471 deacetylation exhibited a potent oncogenic ***,Fascin-K471 acetylation reduced filopodial length and density,and lifespan of ESCC cells,while its deacetylation produced the opp

关键词： acetylation actin-bundling esophageal cancer fascin filopodium formation P300/CBPassociated factor(PCAF) tumor metastasis

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Long non-coding RNAs in cancer

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Science china(Life sciences) 2012年第12期55卷 1120-1124页

作者： GONG Zhaojian zhang ShanShan zhang WenLing HUANG HongBin LI Qiao DENG Hao ma jian ZHOU Ming XIANG Juan Juan WU MingHua LI XiaYu XIONG wei LI XiaoLing LI Yong ZENG ZhaoYang LI GuiYuan Hunan Key laboratory of Nonresolving Inflammation and Cancer Disease Genome Research Center the Third Xiangya Hospital Central South University Changsha 410013 China Key laboratory of Carcinogenesis of Ministry of Health Key laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education Cancer Research Institute Central South University Changsha 410078 China Department of Stomatology the Second Xiangya Hospital Central South University Changsha 410011 China Department of Stomatology Xiangya Hospital Central South University Changsha 410008 China Key laboratory of lnformation System Engineering National University of Defense Technology Changsha 410073 China Department of biochemistry and molecular biology Center for Genetics and Molecular Medicine School of Medicine University of Louisville Louisville KY 40202 USA

Long non-coding RNAs （lncRNAs） are a group of RNA transcripts that exceed 200 nt in length, yet lack significant open reading frames （ORFs） [1-4]. In contrast to small non-coding RNAs （ncRNAs）, such as microRNAs （miR- NAs） [4-23], small interfering RNAs （siRNAs） [24-31] and transfer RNAs （tRNAs） [32-34], there are thousands of IncRNA genes discovered during the past three years in the human genome and most of their functions remain elusive. The long nucleotide chain of lncRNAs can either form a complex spatial structure and interact with protein factors, or provide a large segment for the concurrent binding of many molecules that collectively participate in genomic imprinting, X-chromosome silencing, chromosome modifi- cation, intranuclear transport, transcriptional activation and interference, thereby regulating cell growth, differentiation, development, senescence and death [35].

关键词：非编码RNA tRNA基因 siRNAs 癌症小分子RNA 转录激活开放阅读框转移RNA

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Biomarkers of aging

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Science china(Life sciences) 2023年第5期66卷 893-1066页

作者： Aging Biomarker Consortium Hainan Bao jiani Cao Mengting Chen Min Chen wei Chen Xiao Chen Yanhao Chen Yu Chen Yutian Chen Zhiyang Chen Jagadish K Chhetri yingjie Ding Junlin Feng Jun Guo Mengmeng Guo Chuting He Yujuan Jia Haiping jiang ying Jing Dingfeng Li Jiaming Li Jingyi Li Qinhao Liang Rui Liang Feng Liu Xiaoqian Liu Zuojun Liu Oscar Junhong Luo jianwei Lv Jingyi ma Kehang mao Jiawei Nie Xinhua Qiao Xinpei Sun Xiaoqiang Tang jianfang wang Qiaoran wang Siyuan wang Xuan wang Yaning wang Yuhan wang Rimo Wu Kai Xia Fu-Hui Xiao Lingyan Xu yingying Xu Haoteng Yan Liang Yang Ruici Yang Yuanxin Yang Yilin ying Le zhang weiwei zhang Wenwan zhang Xing zhang Zhuo zhang Min Zhou Rui Zhou Qingchen Zhu Zhengmao Zhu Feng Cao Zhongwei Cao Piu Chan Chang Chen Guobing Chen Hou-Zao Chen Jun Chen weimin Ci Bi-Sen Ding Qiurong Ding Feng Gao Jing-Dong JHan Kai Huang Zhenyu Ju Qing-Peng Kong Ji Li jian Li Xin Li Baohua Liu Feng Liu Lin Liu Qiang Liu Qiang Liu Xingguo Liu Yong Liu Xianghang Luo Shuai ma Xinran ma Zhiyong mao Jing Nie Yaojin Peng Jing Qu Jie Ren Ruibao Ren Moshi Song Zhou Songyang Yi Eve Sun Yu Sun Mei Tian Shusen wang Si wang Xia wang Xiaoning wang Yan-jiang wang Yunfang wang Catherine CL Wong Andy Peng Xiang Yichuan Xiao Zhengwei Xie Daichao Xu Jing Ye Rui Yue Cuntai zhang Hongbo zhang Liang zhang weiqi zhang Yong zhang Yun-Wu zhang Zhuohua zhang Tongbiao Zhao Yuzheng Zhao Dahai Zhu weiguo Zou Gang Pei Guang-Hui Liu Aging Biomarker Consortium(ABC) Beijing 100101China CAS Key laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China State Key laboratory of Stem cell and Reproductive biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Department of Dermatology Xiangya HospitalCentral South UniversityChangsha 410008China Hunan Key laboratory of Aging biology Xiangya HospitalCentral South UniversityChangsha 410008China National Clinical research center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410008China Clinic center of Human Gene research Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Hubei Clinical research center of Metabolic and Cardiovascular Disease Huazhong University of Science and TechnologyWuhan 430022China Hubei Key laboratory of Metabolic Abnormalities and Vascular Aging Huazhong University of Science and TechnologyWuhan 430022China Stem cell Translational research center Tongji HospitalTongji University School of MedicineShanghai 200065China Department of Nuclear Medicine Daping HospitalThird Military Medical UniversityChongqing 400042China CAS Key laboratory of Nutrition Metabolism and Food SafetyShanghai Institute of Nutrition and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China shanghai Key laboratory of maternal Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchShanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China The Department of Endovascular Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Key laboratory of Regenerative Medicine of Ministry of Education Institute of Ageing and Regenerative MedicineJ

Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological *** a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly *** immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this ***,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory *** fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.

关键词： aging senescence biomarker clock

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DCK confers sensitivity of DCTD-positive cancer cells to oxidized methylcytidines

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Protein & cell 2023年第07期 534-539页

作者： Ya-Hui Zhao wei jiang Hai Gao Guo-Zheng Pang Yu-Shuang Wu Yuan-Xian wang Meng-Yao Sheng Jia-ying Xie Wan-Ling Wu Zhi-jian Ji Ya-Rui Du Lei zhang Xiao-Qin wang Colum P.Walsh Hai jiang Guo-Liang Xu Dan Zhou shanghai Key laboratory of Medical Epigenetics Laboratory of Cancer Epigenetics Institutes of Biomedical Sciences Medical College of Fudan University Chinese Academy of Medical Sciences (RU069) State Key laboratory of molecular biology Institute of Biochemistry and Cell Biology Center for Excellence in Molecular Cell Science Chinese Academy of Sciences center for Medical research and Innovation Shanghai Pudong Hospital Fudan University Department of Hematology Huashan Hospital of Fudan University Department of Chemistry and institutes of Biomedical Science Shanghai Medical College Fudan University Genomic Medicine research Group Biomedical Sciences Ulster University Centre for research and Development Region G?vleborg/Uppsala University

Dear Editor,Cytidine analogs,such as decitabine (DAC) and cytarabine (ara-C),have been widely used in the clinical treatment for several cancer types,including myelodysplastic syndrome and acute myeloid leukemia (AML;Appelbaum et al.1999;Saba 2007).However,drug resistance causing treatment failure and disease relapse is an unresolved problem to *** cancer cells rely on the salvage enzymes cytidine deaminase (CDA) and dCMP deaminase (DCTD) to inactivate these cytidine derivative drugs by deamination (Jamieson et al.1987;Ebrahem et al.2012).It is imperative to develop new categories of chemotherapeutic nucleosides to overcome the drug resistance caused by such increased cellular deamination activity.

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L6细胞胰岛素抵抗的骨骼肌细胞模型

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中国组织工程研究与临床康复 2009年第2期13卷 248-251页

作者：杨亮迟戈张俊王良君刘丽娜樊淼刘海东李伟伟张健飞杨菁隋鸿锦辽宁医学院基础学院解剖教研室辽宁省锦州市121000 辽宁省食品药品监督管理局技术审评中心辽宁省沈阳市110001 大连医科大学解剖教研室辽宁省大连市116044 辽宁医学院基础学院生物化学与分子生物学教研室辽宁省锦州市121000

背景:在胰岛素抵抗的细胞模型中,以游离脂肪酸诱导3T3-L1脂肪细胞和高胰岛素诱导的HepG2肝癌细胞最为常见,对分布最为广泛靶组织骨骼肌的胰岛素抵抗模型报道较少。目的:拟使用L6细胞株建立胰岛素抵抗的骨骼肌细胞模型。设计、时间及地点... 详细信息

背景:在胰岛素抵抗的细胞模型中,以游离脂肪酸诱导3T3-L1脂肪细胞和高胰岛素诱导的HepG2肝癌细胞最为常见,对分布最为广泛靶组织骨骼肌的胰岛素抵抗模型报道较少。目的:拟使用L6细胞株建立胰岛素抵抗的骨骼肌细胞模型。设计、时间及地点:细胞学体外观察,于2007-06/2008-05在辽宁医学院生物化学与分子生物学教研室完成。材料:L6细胞株由中国协和医科大学细胞中心提供。α-MEM培养基为美国Gibco公司产品。方法:复苏后的L6细胞置于α-MEM培养基中诱导培养14d,以考马斯亮蓝染色观察肌管出现来确定L6成肌细胞株分化完成。将分化后的细胞建立胰岛素抵抗模型,按1×106/孔接种于24孔板内,用含体积分数为0.02胎牛血清的α-MEM培养,以L6细胞贴满24孔板的板底为宜。换液后,向各孔内分别加入含体积分数为0.02牛血清白蛋白的α-MEM无血清培养基饥饿培养5h。设立2组,实验组的板孔内加入含1×10-7mol/L胰岛素的HEPES缓冲液(136mmol/LNaCl,4.7mmol/LKCl,1.25mmol/LMgSO4,1.2mmol/LCaCl2,0.2%牛血清白蛋白,20mmol/LHEPES,pH7.4)孵育1h;对照组的板孔内加入不含胰岛素的HEPES缓冲液孵育1h。弃上清后用HBS缓冲液冲洗,每孔内分别加入含0.1mol/L葡萄糖的HBS缓冲液100μL,孵育10min后取出置于冰板上快速回收上清。主要观察指标:考马斯亮蓝染色观察L6细胞出现肌管结构情况,葡萄糖氧化酶法检测上清中葡萄糖浓度。结果:诱导前L6细胞未见肌性结构出现,诱导分化后L6细胞内出现肌管结构。使用α-MEM无血清培养基饥饿培养1,3h,两组上清中葡萄糖浓度基本相似(P>0.05);使用α-MEM无血清培养基饥饿培养5h后,实验组上清中葡萄糖浓度明显高于对照组(P1×10-7mol/L的刺激下可形成胰岛素抵抗的骨骼肌细胞模型。

关键词： L6骨骼肌细胞模型 α-MEM 胰岛素抵抗

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骨髓间充质干细胞移植后2型糖尿病鼠血糖及肾脏病变的改善

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中国组织工程研究与临床康复 2009年第10期13卷 1872-1876页

作者：刘伯轩刘师伟王建华樊彩兰李晶李华青岳晓华张悦红刘卓拉牛勃山西医科大学生物化学与分子生物学教研室山西省太原市030001 山西医科大学第二附属医院内分泌科山西省太原市030001 首都儿科研究所生物技术室北京市100020 山西医科大学第二附属医院呼吸科山西省太原市030001

背景:胰岛细胞移植可改善胰岛功能,但其来源匮乏。骨髓间充质干细胞可被诱导分化成胰岛细胞,在糖尿病足、糖尿病心肌病、糖尿病神经病变中具有较强的组织修复能力。目的:观察骨髓间充质干细胞移植后在2型糖尿病模型鼠胰腺、肾脏组织中... 详细信息

背景:胰岛细胞移植可改善胰岛功能,但其来源匮乏。骨髓间充质干细胞可被诱导分化成胰岛细胞,在糖尿病足、糖尿病心肌病、糖尿病神经病变中具有较强的组织修复能力。目的:观察骨髓间充质干细胞移植后在2型糖尿病模型鼠胰腺、肾脏组织中的存活及转归,及对血糖及肾脏病变的改善。设计、时间及地点:细胞学体内实验,于2008-02/07在山西医科大学生物化学与分子生物学教研室完成。材料:雄性Wistar大鼠由山西医科大学实验动物中心提供,造模使用的链脲佐菌素为Sigma公司产品。方法:取1只大鼠体外分离培养骨髓间充质干细胞,反复贴壁纯化,传至第3代行BrdU标记后用于移植。60只大鼠随机分为3组,模型对照组、细胞移植组向标准混合饲料中添加含体积分数为0.1的猪油和蛋黄高脂成分,喂养2个月后向大鼠腹腔内注射链脲佐菌素,血糖≥16.77mmol/L且维持3d稳定代表成功建立2型糖尿病模型。正常组采用标准混合饲料喂养2个月后,向大鼠腹腔内注射等容积柠檬酸缓冲液。造模成功后,细胞移植组经尾静脉注射骨髓间充质干细胞悬液0.5mL(细胞数1×106个),其余两组注射等量PBS液。主要观察指标:各组大鼠血糖浓度及三酰甘油、胰岛素水平的变化,肾组织病理学变化,细胞在肾脏及胰腺组织中的分布。结果:与移植前比较,移植后7,14,21d模型对照组血糖浓度无明显变化,细胞移植组血糖浓度明显下降(P1);移植后21d与正常组比较,模型对照组及细胞移植组三酰甘油水平均显著升高(P1),胰岛素水平均显著降低(P1),但细胞移植组胰岛素降低幅度小于模型对照组(P1)。糖原染色结果示模型对照组肾小球发生肥大,细胞移植组肾小球基质变薄,肥大得以改善。胰岛素免疫荧光染色后,模型对照组胰岛细胞明显减少,而细胞移植组胰岛细胞增加,在胰腺、肾脏组织中均可见BrdU标记的阳性细胞。结论:经尾静脉注射骨髓间充质干细胞可定位于2型糖尿病大鼠胰腺及肾脏,并对其进行组织修复,同时可降低血糖,增加胰岛素分泌。

关键词：骨髓间充质干细胞血糖肾小球肥大 2型糖尿病

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