AIM: To study the mechanisms responsible for inactivation of a novel esophageal cancer related gene 4 (ECRG4) in esophageal squamous cell carcinoma (ESCC).
METHODS: A pair of primers was designed to amplify a 220 bp f...AIM: To study the mechanisms responsible for inactivation of a novel esophageal cancer related gene 4 (ECRG4) in esophageal squamous cell carcinoma (ESCC).
METHODS: A pair of primers was designed to amplify a 220 bp fragment, which contains 16 CpG sites in the core promoter region of the ECRG 4 gene. PCR products of bisulfite-modified CpG islands were analyzed by denaturing high-performance liquid chromatography (DHPLC), which were confirmed by DNA sequencing. The methylation status of ECRG 4 promoter in 20 cases of esophageal cancer and the adjacent normal tissues, 5 human tumor cell lines (esophageal cancer cell line-NEC, EC109, EC9706; gastric cancer cell line- GLC; human embryo kidney cell line-Hek293)and 2 normal esophagus tissues were detected. The expression level of the ECRG 4 gene in these samples was examined by RT-PCR.
RESULTS: The expression level of ECRG 4 gene was varied.Of 20 esophageal cancer tissues, nine were unexpressed,six were lowly expressed and five were highly expressed compared with the adjacent tissues and the 2 normal esophageal epithelia. In addition, 4 out of the 5 human cell lines were also unexpressed. A high frequency of methylation was revealed in 12 (8 unexpressed and 4 lowly expressed)of the 15 (80%) downregulated cancer tissues and 3 of the 4 unexpressed cell lines. No methylation peak was observed in the two highly expressed normal esophageal epithelia and the methylation frequency was low (3/20) among the 20 cases in the highly expressed adjacent tissues. The methylation status of the samples was consistent with the result of DNA sequencing.
CONCLUSION: These results indicate that the inactivation of ECRG 4gene by hypermethylation is a frequent molecular event in ESCC and may be involved in the carcinogenesis of this cancer.展开更多
Neurogenesis decline in hippocampal dentate gyrus(DG)participates in stress-induced depressive-like behaviors,but the underlying mechanism remains poorly understood.Here,we observed low-expression of NOD-like receptor...Neurogenesis decline in hippocampal dentate gyrus(DG)participates in stress-induced depressive-like behaviors,but the underlying mechanism remains poorly understood.Here,we observed low-expression of NOD-like receptor family pyrin domain containing 6(NLRP6)in hippocampus of stress-stimulated mice,being consistent with high corticosterone level.NLRP6 was found to be abundantly expressed in neural stem cells(NSCs)of DG.Both Nlrp6 knockout(Nlrp6^(-/-))and NSCconditional Nlrp6 knockout(Nlrp6CKO)mice were susceptible to stress,being more likely to develop depressive-like behaviors.Interestingly,NLRP6 was required for NSC proliferation in sustaining hippocampal neurogenesis and reinforcing stress resilience during growing up.Nlrp6 deficiency promoted esophageal cancer-related gene 4(ECRG4)expression and caused mitochondrial dysfunction.Corticosterone as a stress factor significantly down-regulated NLRP6 expression,damaged mitochondrial function and suppressed cell proliferation in NSCs,which were blocked by Nlrp6 overexpression.ECRG4 knockdown reversed corticosterone-induced NSC mitochondrial function and cell proliferation disorders.Pioglitazone,a well-known clinical drug,up-regulated NLRP6 expression to inhibit ECRG4 expression in its protection against corticosterone-induced NSC mitochondrial dysfunction and proliferation restriction.In conclusion,this study demonstrates that NLRP6 is essential to maintain mitochondrial homeostasis and proliferation in NSCs,and identifies NLRP6 as a promising therapeutic target for hippocampal neurogenesis decline linked to depression.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
食管癌相关基因4(esophageal cancer related gene 4,ECRG4)是一个在基因表达和蛋白作用方式方面独具特点的抑癌基因。生物信息学分析显示ECRG4的基因结构在不同种属中十分保守,提示其在维持细胞的正常生理功能方面可能发挥着重要作用...食管癌相关基因4(esophageal cancer related gene 4,ECRG4)是一个在基因表达和蛋白作用方式方面独具特点的抑癌基因。生物信息学分析显示ECRG4的基因结构在不同种属中十分保守,提示其在维持细胞的正常生理功能方面可能发挥着重要作用。本文对ECRG4的生物学背景和其在生理条件及病理条件下的表达情况和功能进行了综述,并对ECRG4在精准医疗中的可能作用进行了讨论,以期为以ECRG4为靶点的诊断和治疗提供可能的线索。展开更多
目的研究甲状腺乳头状癌组织中ECRG4基因的表达水平,及ECRG4在甲状腺乳头状癌中的作用。方法收取甲状腺乳头状癌组织30例作为病例组,选取相对应的20例正常甲状腺组织作为对照组,通过实时荧光定量PCR法(QRT-PCR)以及免疫组织化学法,检测E...目的研究甲状腺乳头状癌组织中ECRG4基因的表达水平,及ECRG4在甲状腺乳头状癌中的作用。方法收取甲状腺乳头状癌组织30例作为病例组,选取相对应的20例正常甲状腺组织作为对照组,通过实时荧光定量PCR法(QRT-PCR)以及免疫组织化学法,检测ECRG4基因及其蛋白在甲状腺组织中的表达情况。结果 QRT-PCR检测结果显示,ECRG4 m RNA在甲状腺乳头状癌中呈现高表达,其表达水平明显高于对照组(P<0.01);免疫组织化学结果也显示,甲状腺乳头状癌中ECRG4蛋白呈现出高表达,显著高于对照组(P<0.01)。结论甲状腺乳头状癌组织中ECRG4基因及其蛋白呈现高表达,ECRG4在甲状腺乳头状癌中可能为一个促癌基因,其在甲状腺癌的发生及发展过程中起着重要作用。展开更多
人类食管癌相关基因4（esophageal cancer related gene 4, ECRG4）是一种潜在的抑癌基因，该基因在食管鳞状细胞癌[1,2,3,4]、乳腺癌[5]、结肠癌[6,7]、胶质瘤[6,8]、肾癌[9]、喉癌[10]等多种肿瘤细胞中具有抑癌作用，并且在这些肿瘤...人类食管癌相关基因4（esophageal cancer related gene 4, ECRG4）是一种潜在的抑癌基因，该基因在食管鳞状细胞癌[1,2,3,4]、乳腺癌[5]、结肠癌[6,7]、胶质瘤[6,8]、肾癌[9]、喉癌[10]等多种肿瘤细胞中具有抑癌作用，并且在这些肿瘤细胞中低表达或者不表达，但在人类正常组织中广泛表达。目前研究发现，ECRG4的抗肿瘤作用可能包括阻滞肿瘤细胞周期、促进细胞凋亡、抑制细胞迁移与侵袭等。本文就ECRG4抗肿瘤的分子机制进行综述，并讨论该基因在肿瘤治疗方面的应用前景。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
基金grant from State Key Basic Program(G1998051204)the Ministry of Education,China
文摘AIM: To study the mechanisms responsible for inactivation of a novel esophageal cancer related gene 4 (ECRG4) in esophageal squamous cell carcinoma (ESCC).
METHODS: A pair of primers was designed to amplify a 220 bp fragment, which contains 16 CpG sites in the core promoter region of the ECRG 4 gene. PCR products of bisulfite-modified CpG islands were analyzed by denaturing high-performance liquid chromatography (DHPLC), which were confirmed by DNA sequencing. The methylation status of ECRG 4 promoter in 20 cases of esophageal cancer and the adjacent normal tissues, 5 human tumor cell lines (esophageal cancer cell line-NEC, EC109, EC9706; gastric cancer cell line- GLC; human embryo kidney cell line-Hek293)and 2 normal esophagus tissues were detected. The expression level of the ECRG 4 gene in these samples was examined by RT-PCR.
RESULTS: The expression level of ECRG 4 gene was varied.Of 20 esophageal cancer tissues, nine were unexpressed,six were lowly expressed and five were highly expressed compared with the adjacent tissues and the 2 normal esophageal epithelia. In addition, 4 out of the 5 human cell lines were also unexpressed. A high frequency of methylation was revealed in 12 (8 unexpressed and 4 lowly expressed)of the 15 (80%) downregulated cancer tissues and 3 of the 4 unexpressed cell lines. No methylation peak was observed in the two highly expressed normal esophageal epithelia and the methylation frequency was low (3/20) among the 20 cases in the highly expressed adjacent tissues. The methylation status of the samples was consistent with the result of DNA sequencing.
CONCLUSION: These results indicate that the inactivation of ECRG 4gene by hypermethylation is a frequent molecular event in ESCC and may be involved in the carcinogenesis of this cancer.
基金National Key R&D Program of China(2022YFC3500303)National Natural Science Foundation of China(81991522)partly by the Open Project of State Key Laboratory of Natural Medicine,No.SKLNMKF202204,China。
文摘Neurogenesis decline in hippocampal dentate gyrus(DG)participates in stress-induced depressive-like behaviors,but the underlying mechanism remains poorly understood.Here,we observed low-expression of NOD-like receptor family pyrin domain containing 6(NLRP6)in hippocampus of stress-stimulated mice,being consistent with high corticosterone level.NLRP6 was found to be abundantly expressed in neural stem cells(NSCs)of DG.Both Nlrp6 knockout(Nlrp6^(-/-))and NSCconditional Nlrp6 knockout(Nlrp6CKO)mice were susceptible to stress,being more likely to develop depressive-like behaviors.Interestingly,NLRP6 was required for NSC proliferation in sustaining hippocampal neurogenesis and reinforcing stress resilience during growing up.Nlrp6 deficiency promoted esophageal cancer-related gene 4(ECRG4)expression and caused mitochondrial dysfunction.Corticosterone as a stress factor significantly down-regulated NLRP6 expression,damaged mitochondrial function and suppressed cell proliferation in NSCs,which were blocked by Nlrp6 overexpression.ECRG4 knockdown reversed corticosterone-induced NSC mitochondrial function and cell proliferation disorders.Pioglitazone,a well-known clinical drug,up-regulated NLRP6 expression to inhibit ECRG4 expression in its protection against corticosterone-induced NSC mitochondrial dysfunction and proliferation restriction.In conclusion,this study demonstrates that NLRP6 is essential to maintain mitochondrial homeostasis and proliferation in NSCs,and identifies NLRP6 as a promising therapeutic target for hippocampal neurogenesis decline linked to depression.
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.
文摘食管癌相关基因4(esophageal cancer related gene 4,ECRG4)是一个在基因表达和蛋白作用方式方面独具特点的抑癌基因。生物信息学分析显示ECRG4的基因结构在不同种属中十分保守,提示其在维持细胞的正常生理功能方面可能发挥着重要作用。本文对ECRG4的生物学背景和其在生理条件及病理条件下的表达情况和功能进行了综述,并对ECRG4在精准医疗中的可能作用进行了讨论,以期为以ECRG4为靶点的诊断和治疗提供可能的线索。
基金the National Undergraduates Innovating Experimentation Project(Grant No.201310350015)the program of Natural Science Foundation of Zhejiang Province(No.Y2100248)+3 种基金the program of Science and Technology Department of Zhejiang Province(No.2009C33155)The program of Health Bureau of Zhejiang Province(No.2009A218)The program of Science and Technology Divison of Taizhou Municipality(No.102KY15)The program of Zhejiang Provincial Administration of Traditional Chinese Medicine(No.2011ZA113)~~
文摘目的研究甲状腺乳头状癌组织中ECRG4基因的表达水平,及ECRG4在甲状腺乳头状癌中的作用。方法收取甲状腺乳头状癌组织30例作为病例组,选取相对应的20例正常甲状腺组织作为对照组,通过实时荧光定量PCR法(QRT-PCR)以及免疫组织化学法,检测ECRG4基因及其蛋白在甲状腺组织中的表达情况。结果 QRT-PCR检测结果显示,ECRG4 m RNA在甲状腺乳头状癌中呈现高表达,其表达水平明显高于对照组(P<0.01);免疫组织化学结果也显示,甲状腺乳头状癌中ECRG4蛋白呈现出高表达,显著高于对照组(P<0.01)。结论甲状腺乳头状癌组织中ECRG4基因及其蛋白呈现高表达,ECRG4在甲状腺乳头状癌中可能为一个促癌基因,其在甲状腺癌的发生及发展过程中起着重要作用。
文摘人类食管癌相关基因4（esophageal cancer related gene 4, ECRG4）是一种潜在的抑癌基因，该基因在食管鳞状细胞癌[1,2,3,4]、乳腺癌[5]、结肠癌[6,7]、胶质瘤[6,8]、肾癌[9]、喉癌[10]等多种肿瘤细胞中具有抑癌作用，并且在这些肿瘤细胞中低表达或者不表达，但在人类正常组织中广泛表达。目前研究发现，ECRG4的抗肿瘤作用可能包括阻滞肿瘤细胞周期、促进细胞凋亡、抑制细胞迁移与侵袭等。本文就ECRG4抗肿瘤的分子机制进行综述，并讨论该基因在肿瘤治疗方面的应用前景。
