Esophageal cancer-related gene-4(Ecrg4)is cloned from the normal epithelium of the esophagus.It is constitutively expressed in quiescent epithelial cells and downregulated during tumorigenesis,and Ecrg4 expression lev...Esophageal cancer-related gene-4(Ecrg4)is cloned from the normal epithelium of the esophagus.It is constitutively expressed in quiescent epithelial cells and downregulated during tumorigenesis,and Ecrg4 expression levels are inversely correlated with the malignant phenotype of tumor cells,validating that Ecrg4 is a real tumor suppressor gene.Unlike other tumor suppressor genes that usually encode membrane or intracellular proteins,Ecrg4 encodes a 148-amino acid pre-pro-peptide that is tethered on the cell surface in epithelial cells,specialized epithelial cells,and human leukocytes,where it can be processed tissue dependently into several small peptides upon cell activation.Ecrg4 is expressed in a wide variety of other cells/tissues,including cardiomyocytes and conduction system of the heart,,the glomus cells of the carotid body,adrenal glands,choroid plexus,and leukocytes among others,where it exerts distinct functions,such as promoting/suppressing inflammation,inducing neuron senescence,stimulating the hypothalamus--pituitary--adrenal axis,maintaining the stemness of stem cells,participating in the rhythm and rate control of the heart,and possibly gauging the responsiveness of the cardiovascular system(CVS)to hypoxia,in addition to tumor suppression.Here,we briefly review the latest discoveries on Ecrg4 and its underlying molecular mechanisms as a tumor suppressor and focus on the emerging roles of Ecrg4 in the CVS.展开更多
目的探讨脑出血(intracerebral hemorrhage,ICH)患者术后脑脊液(CSF)中食管癌相关基因4(ECRG4)与S100钙结合蛋白B(S100B)表达水平与格拉斯哥昏迷评分(Glasgow coma scale,GCS)和巴氏指数(barthel index,BI)的相关性,及其在脑出血患者术...目的探讨脑出血(intracerebral hemorrhage,ICH)患者术后脑脊液(CSF)中食管癌相关基因4(ECRG4)与S100钙结合蛋白B(S100B)表达水平与格拉斯哥昏迷评分(Glasgow coma scale,GCS)和巴氏指数(barthel index,BI)的相关性,及其在脑出血患者术后神经功能康复中的临床应用价值。方法选择2017年1月~2019年12月入住陕西省人民医院神经外科治疗的基底节区ICH患者30例,采用酶联免疫吸附法(ELISA)检测10例对照组、10例腰大池引流组和10例腰椎穿刺组患者ICH术后ECRG4与S100B蛋白水平,进行GCS和BI评分,并进行相关性分析。结果术后7天时,对照组ECRG4(1.14±0.39pg/ml)低于引流组(15.50±0.28 pg/ml)和穿刺组(10.71±0.89pg/ml),对照组S100B(0.550±0.310ng/ml)水平高于引流组(0.154±0.025ng/ml)与穿刺组(0.192±0.030ng/ml),引流组两者表达水平与穿刺组比较,差异均有统计学意义(t=11.630,28.120,均P<0.05)。术后7天时,引流组与穿刺组GCS(11.62±1.71,10.19±1.41)及BI(43.24±10.05,40.64±10.10)评分均高于对照组(GCS:7.07±1.43,BI:21.73±6.45),差异具有统计学意义(t=7.466,4.180,P<0.05)。结论ECRG4与S100B蛋白在脑出血患者脑脊液中的变化趋势与GCS和BI评分具有相关性,两者联合检测,有助于调整治疗方案,从而降低患者神经功能障碍的发生,改善预后。展开更多
目的:探讨体外沉默Kruppel样因子4(Kruppel like factor 4,KLF4)基因的表达对食管癌KYSE140细胞增殖及迁移的影响。方法:Western blotting法检测人食管癌细胞株KYSE140、KYSE150、EC109及EC9706及食管永生化细胞NE3中KLF4蛋白的表达,化...目的:探讨体外沉默Kruppel样因子4(Kruppel like factor 4,KLF4)基因的表达对食管癌KYSE140细胞增殖及迁移的影响。方法:Western blotting法检测人食管癌细胞株KYSE140、KYSE150、EC109及EC9706及食管永生化细胞NE3中KLF4蛋白的表达,化学合成2对靶向KLF4的siRNA(KLF4-siRNA1,KLF4-siRNA2),并设对照siRNA(Ctrl-siRNA),分别体外转染至高表达KLF4的食管癌KYSE140细胞中,形成KLF4-siRNA1-KYSE140、KLF4-siRNA2-KYSE140及Ctrl-siRNA-KYSE140细胞,通过MTT实验、Transwell实验分别检测转染后食管癌KYSE140细胞的增殖及迁移。结果:食管癌细胞株KYSE140中KLF4蛋白的表达明显高于KYSE150、EC109及EC9706细胞株[(5.62±0.02)vs(1.71±0.23)、(3.24±0.35)、(3.16±0.41),均P<0.05]。KLF4-siRNA1-KYSE140、KLF4-siRNA2-KYSE140与Ctrl-siRNA-KYSE140细胞相比,KLF4蛋白表达明显降低[(0.49±0.18)、(0.32±0.09)vs(0.98±0.19),均P<0.05],细胞增殖能力明显增高[(1.2±0.8)、(1.4±0.1)vs(0.6±0.1),均P<0.05],迁移细胞数量也明显增加[(780±22)、(475±25)vs(83±17)个,P<0.05]。结论:KLF4在人食管癌细胞的增殖和迁移过程中起着负调控作用。展开更多
目的探讨人食管癌相关基因4(esophageal cancer related gene4,ECRG4)蛋白的亚细胞定位和重组ECRG4蛋白的体外抑癌功能。方法用激光扫描共聚焦显微镜成像法和Western blot方法检测ECRG4蛋白的定位;用MTT方法检测纯化的重组ECRG4蛋白的...目的探讨人食管癌相关基因4(esophageal cancer related gene4,ECRG4)蛋白的亚细胞定位和重组ECRG4蛋白的体外抑癌功能。方法用激光扫描共聚焦显微镜成像法和Western blot方法检测ECRG4蛋白的定位;用MTT方法检测纯化的重组ECRG4蛋白的体外抑癌功能。结果激光扫描共聚焦显微镜成像显示,内源性和外源性ECRG4蛋白主要定位在细胞质。Western blot方法在细胞无血清培养液中检测到ECRG4蛋白存在,提示ECRG4蛋白是分泌蛋白。纯化的重组ECRG4蛋白可以体外抑制EC9706细胞的增殖,抑制率随着ECRG4蛋白浓度增加而升高,成剂量-效应关系(P<0.05)。结论重组人ECRG4蛋白体外抑制肿瘤细胞增殖,可以作为ESCC的潜在治疗药物。展开更多
Given the rapid development in precision medicine, tremendous efforts have been devoted to discovering new biomarkers for disease diagnosis and treatment. Esophageal cancer-related gene-4 (ECRG4),which is initially kn...Given the rapid development in precision medicine, tremendous efforts have been devoted to discovering new biomarkers for disease diagnosis and treatment. Esophageal cancer-related gene-4 (ECRG4),which is initially known as a new candidate tumor suppressor gene, is emerging as a sentinel molecule for gauging tissue homeostasis. ECRG4 is unique in its cytokine-like functional pattern and epigenetically-regulated gene expression pattern. The gene can be released from the cell membrane upon activation and detected in liquid biopsy, thus offering considerable potential in precision medicine. This review provides an updated summary on the biology of ECRG4, with emphasis on its important roles in cancer diagnosis and therapy. The future perspectives of ECRG4 as a potential molecular marker in precision medicine are also discussed in detail.展开更多
基金This study was funded by the Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province,Southwest Medical University(No.xtcx-2016-16)the National Natural Science Foundation o f China(No.81770336)a seeding grant from Southwest Medical University.
文摘Esophageal cancer-related gene-4(Ecrg4)is cloned from the normal epithelium of the esophagus.It is constitutively expressed in quiescent epithelial cells and downregulated during tumorigenesis,and Ecrg4 expression levels are inversely correlated with the malignant phenotype of tumor cells,validating that Ecrg4 is a real tumor suppressor gene.Unlike other tumor suppressor genes that usually encode membrane or intracellular proteins,Ecrg4 encodes a 148-amino acid pre-pro-peptide that is tethered on the cell surface in epithelial cells,specialized epithelial cells,and human leukocytes,where it can be processed tissue dependently into several small peptides upon cell activation.Ecrg4 is expressed in a wide variety of other cells/tissues,including cardiomyocytes and conduction system of the heart,,the glomus cells of the carotid body,adrenal glands,choroid plexus,and leukocytes among others,where it exerts distinct functions,such as promoting/suppressing inflammation,inducing neuron senescence,stimulating the hypothalamus--pituitary--adrenal axis,maintaining the stemness of stem cells,participating in the rhythm and rate control of the heart,and possibly gauging the responsiveness of the cardiovascular system(CVS)to hypoxia,in addition to tumor suppression.Here,we briefly review the latest discoveries on Ecrg4 and its underlying molecular mechanisms as a tumor suppressor and focus on the emerging roles of Ecrg4 in the CVS.
文摘目的:探讨体外沉默Kruppel样因子4(Kruppel like factor 4,KLF4)基因的表达对食管癌KYSE140细胞增殖及迁移的影响。方法:Western blotting法检测人食管癌细胞株KYSE140、KYSE150、EC109及EC9706及食管永生化细胞NE3中KLF4蛋白的表达,化学合成2对靶向KLF4的siRNA(KLF4-siRNA1,KLF4-siRNA2),并设对照siRNA(Ctrl-siRNA),分别体外转染至高表达KLF4的食管癌KYSE140细胞中,形成KLF4-siRNA1-KYSE140、KLF4-siRNA2-KYSE140及Ctrl-siRNA-KYSE140细胞,通过MTT实验、Transwell实验分别检测转染后食管癌KYSE140细胞的增殖及迁移。结果:食管癌细胞株KYSE140中KLF4蛋白的表达明显高于KYSE150、EC109及EC9706细胞株[(5.62±0.02)vs(1.71±0.23)、(3.24±0.35)、(3.16±0.41),均P<0.05]。KLF4-siRNA1-KYSE140、KLF4-siRNA2-KYSE140与Ctrl-siRNA-KYSE140细胞相比,KLF4蛋白表达明显降低[(0.49±0.18)、(0.32±0.09)vs(0.98±0.19),均P<0.05],细胞增殖能力明显增高[(1.2±0.8)、(1.4±0.1)vs(0.6±0.1),均P<0.05],迁移细胞数量也明显增加[(780±22)、(475±25)vs(83±17)个,P<0.05]。结论:KLF4在人食管癌细胞的增殖和迁移过程中起着负调控作用。
文摘目的探讨人食管癌相关基因4(esophageal cancer related gene4,ECRG4)蛋白的亚细胞定位和重组ECRG4蛋白的体外抑癌功能。方法用激光扫描共聚焦显微镜成像法和Western blot方法检测ECRG4蛋白的定位;用MTT方法检测纯化的重组ECRG4蛋白的体外抑癌功能。结果激光扫描共聚焦显微镜成像显示,内源性和外源性ECRG4蛋白主要定位在细胞质。Western blot方法在细胞无血清培养液中检测到ECRG4蛋白存在,提示ECRG4蛋白是分泌蛋白。纯化的重组ECRG4蛋白可以体外抑制EC9706细胞的增殖,抑制率随着ECRG4蛋白浓度增加而升高,成剂量-效应关系(P<0.05)。结论重组人ECRG4蛋白体外抑制肿瘤细胞增殖,可以作为ESCC的潜在治疗药物。
基金the Major Program Development Project of the National Natural Science Foundation of China (No.30600492)the Natural Science Foundation of Shaanxi Province (No.2016JM 3010)+2 种基金Xiangyang Science and Technology (Intellectual Property) Bureau (2016 file No.73)the Natural Science Foundation of Hubei Province (No.2014CFC1154)the Teachers’ Scientific A bility Cultivation Foundation of Hubei University of Arts and Science (No.2017KYPY004).
文摘Given the rapid development in precision medicine, tremendous efforts have been devoted to discovering new biomarkers for disease diagnosis and treatment. Esophageal cancer-related gene-4 (ECRG4),which is initially known as a new candidate tumor suppressor gene, is emerging as a sentinel molecule for gauging tissue homeostasis. ECRG4 is unique in its cytokine-like functional pattern and epigenetically-regulated gene expression pattern. The gene can be released from the cell membrane upon activation and detected in liquid biopsy, thus offering considerable potential in precision medicine. This review provides an updated summary on the biology of ECRG4, with emphasis on its important roles in cancer diagnosis and therapy. The future perspectives of ECRG4 as a potential molecular marker in precision medicine are also discussed in detail.
