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Hong Fan - One of the best experts on this subject based on the ideXlab platform.
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Promoter polymorphisms of DNA Methyltransferase 3B and risk of hepatocellular carcinoma.
Biomedical reports, 2013Co-Authors: Yingbin Lao, Chengchegn Zhao, Fengchang Qiao, Hong FanAbstract:Hepatocellular carcinoma (HCC) is one of the most common solid tumors worldwide. Epigenetic changes in gene expression, including DNA methylation and histone modifications, may contribute to the development of HCC. Polymorphisms of the DNA Methyltransferase 3B (DNMT3B) gene may affect the activity of this enzyme and increase the susceptibility to several types of cancer, including HCC. To confirm this hypothesis, we investigated the association between single-nucleotide polymorphisms-149C>T (rs2424913) and -579G>T (rs1569686) in the promoter region of DNMT3B and the risk of HCC. DNMT single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism in 108 HCC patients and 240 healthy controls matched for age, gender and ethnicity. The DNMT3B-149 TT genotype was not significantly associated with an increased risk of HCC. The frequency of DNMT3B-149C was 0.46% in HCC patients and 1.39% in healthy individuals, whereas the frequency of DNMT3B-579G was 8.33% in HCC patients and 10.42% in healthy individuals. No significant differences were observed in the genotype or allelic distribution between HCC patients and controls. In conclusion, DNMT3B-149C>T and -579G>T polymorphisms are not significantly associated with an increased risk of HCC. These results demonstrated that these particular SNPs may not be used as biomarkers to predict susceptibility to HCC.
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Expression pattern and clinical significance of DNA Methyltransferase 3B variants in gastric carcinoma.
Oncology reports, 2010Co-Authors: Fengchang Qiao, Xuemei Qiu, Wen-bin Huang, Zhujiang Zhao, Hong FanAbstract:The aim of this study was to detect the expression pattern of DNA Methyltransferase 3B (DNMT3B) variants in primary gastric cancer (GC) and to explore the clinical significance of DNMT3B variants in gastric carcinogenesis. Specific polymerase chain reaction (PCR) primer sets were designed to distinguish individual DNMT3B variants according to their splicing patterns. Expression levels of DNMT3B variants were assessed by quantitative real-time RT-PCR in gastric cancer tissue, normal gastric mucosae and GC cell lines. The relationship between the expression patterns of the DNMT3B variants and corresponding clinical information was analyzed by observing the expression levels of different variants in the tumors. These results demonstrate that DNMT3B overexpression is related to late phase invasion (P=0.029) and intestinal type (P=0.012) in GC. DNMT3B3 expression was higher in normal tissue, compared to tumor tissue (P=0.033). In contrast, only 18, 32 and 35% of the patient tumors overexpressed DNMT3B1, DNMT3B4 and DNMT3B5, respectively. While taking into account environmental factors (H. pylori, Epstein-Barr virus infection), H. pylori infection elevated DNMT3B1 and DNMT3B3 variants in tumors, while increasing DNMT3B4 in both tumor and non-cancerous tissues. Our findings indicated that the expression of DNMT3B3 is the major splice variant in normal gastric mucosae and may be affected by H. pylori infection. Elevated DNMT3B variants may influence the progression of gastric cancer and may possibly be a powerful indicator for the disease.
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DNMT3B Promoter Polymorphism and Risk of Gastric Cancer
Digestive diseases and sciences, 2009Co-Authors: Hong Fan, Dongsheng Liu, Shu-hong Zhang, Feng ZhangAbstract:To investigate the association of single-nucleotide polymorphism (SNP) in DNA Methyltransferase 3B (DNMT3B) gene and the risk of gastric cancer (GC), we detected -149C>T and -579G>T in the promoter region of the DNMT3B gene by polymerase chain reaction restriction fragment length polymorphism (PCR–RFLP) and DNA sequencing analysis. The DNMT3B genotype was determined in 259 gastric cancer patients and 262 healthy controls that were frequency matched for age and gender. Results showed that individuals with at least one -579G allele were also at significantly decreased risk of gastric cancer [odds ratio (OR), 0.43; 95% confidence interval (CI) 0.26–0.72] compared with those having a -579TT genotype. The -149C>T genotype distribution was irrelevant to the risk of gastric cancer (OR, 1.49; 95% CI, 0.17–17.94) in the studied Chinese population. In addition, data suggested that DNMT3B genetic polymorphism varied among different races, ethnic groups, and geographic areas.
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Promoter polymorphisms of DNMT3B and the risk of colorectal cancer in Chinese: a case-control study
Journal of experimental & clinical cancer research : CR, 2008Co-Authors: Hong Fan, Feng Zhang, Dongsheng Liu, Zhujiang ZhaoAbstract:Background DNA-Methyltransferase-3B (DNMT3B), which plays a role in DNA methylation, is usually aberrant expression involved in carcinogenesis. Polymorphisms of the DNMT3B gene may influence DNMT3B activity on DNA methylation in several cancers, thereby modulating the susceptibility to cancer.
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Identification of potential genes regulated by DNA Methyltransferase 3B in a hepatocellular carcinoma cell line by RNA interference and microarray analysis.
Yi chuan xue bao = Acta genetica Sinica, 2005Co-Authors: Hong Fan, Zhujiang Zhao, Jianqiong Zhang, Wei XieAbstract:Whether DNA Methyltransferase 3B (DNMT3B) is deregulated in hepatocellular carcinoma cell lines is still unclear. The expression levels of DNMT3B protein in normal liver cell line, pericacinoma cell line and hepatocellular carcinoma cell lines were compared by both Western blotting and immunocytochemistry. Long-term downregulated DNMT3B in a hepatocellular carcinoma cell line SMMC-7721 was achieved using a RNAi recombinant plasmid. The suppression of DNMT3B induced by RNA interference was confirmed using semi-quantitative RT-PCR and Western blotting. High throughput cDNA microarray was used to analyze the expression profiling of downstream genes of DNMT3B displayed in the treated cell lines and control. In the result,DNMT3B in hepatocellular carcinoma cell lines was expressed at a significantly higher level compared to those in pericacinoma cell line and normal liver cell line. A specific DNMT3B siRNA stably expressed from a plasmid vector effectively suppressed the expression of DNMT3B in SMMC-7721 cell line. By microarray analysis,26 downregulated genes and 115 upregulated genes have been identified in the DNMT3B knockdown cell line,including some important developmental genes and tumor-related genes such as SNCG, NOTCH1, MBD3, WNT11, MAOA and FACL4. The discovery showed DNMT3B was over-expressed in most hepatocellular carcinoma cell lines examined and may be linked to the carcinogenesis of hepatocytes. An array of candidate genes that are involved in the action of DNMT3B have been identified,including those related to development.
Yae Kanai - One of the best experts on this subject based on the ideXlab platform.
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DNA Methyltransferase 3B expression is associated with poor outcome of stage I testicular seminoma
Histopathology, 2012Co-Authors: Eri Arai, Tohru Nakagawa, Saori Wakai-ushijima, Hiroyuki Fujimoto, Yae KanaiAbstract:Arai E, Nakagawa T, Wakai-Ushijima S, Fujimoto H & Kanai Y (2012) Histopathology 60, E12–E18 DNA Methyltransferase 3B expression is associated with poor outcome of stage I testicular seminoma Aims: To examine in testicular seminomas the expression of DNA Methyltransferase 3B (DNMT3B), which is known to be associated with early embryonic development and carcinogenesis, and to obtain a predictive marker for relapse of stage I seminomas. Methods and results: Immunohistochemical examination of DNMT3B was performed in 88 cases of seminoma, 35 (39.8%) of which showed widely scattered nuclear immunoreactivity for DNMT3B, and 53 (60.2%) of which were completely negative. The incidence of focal DNMT3B expression was higher in stage III seminomas (5/5, 100%) than in stage I (25/70, 35.7%) or stage II (5/13, 38.5%) seminomas (P = 0.011). In stage I seminomas there were no significant correlations between DNMT3B expression and tumour size, invasion of the rete testis, or lymphatic or vascular involvement. Six of 25 cases (24%) showing DNMT3B expression relapsed, whereas only 3/45 cases (6.7%) lacking such expression did so (P = 0.037). Patients with seminomas showing DNMT3B expression had a significantly lower relapse-free survival rate than patients whose tumours lacked this feature (P = 0.0464). Conclusions: Patients with seminomas showing focal DNMT3B expression are at increased risk of relapse, and should be followed up carefully.
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Alterations in gene expression associated with the overexpression of a splice variant of DNA Methyltransferase 3B, DNMT3B4, during human hepatocarcinogenesis
Journal of Cancer Research and Clinical Oncology, 2004Co-Authors: Yae Kanai, Yoshimasa Saito, Saori Ushijima, Setsuo HirohashiAbstract:Purpose Overexpression of a splice variant of DNA Methyltransferase 3B, DNMT3B4, correlates significantly with DNA hypomethylation in pericentromeric satellite regions, which is known to result in centromeric decondensation and enhanced chromosomal recombination in precancerous conditions and hepatocellular carcinomas (HCCs). We aimed to elucidate further the significance of DNMT3B4 during human hepatocarcinogenesis. Methods DNMT3B4-transfected human epithelial 293 cells were characterized using growth rate measurements, gene expression microarray, and quantitative reverse transcription-polymerase chain reaction (RT-PCR) analyses. RT-PCR was also performed on eight normal liver specimens, 45 noncancerous liver specimens showing chronic hepatitis or cirrhosis, which are considered to be precancerous conditions, and 56 HCCs. Results The growth rate of the DNMT3B4 transfectants was about double that of mock-transfectants. Induction of signal transducer and activator of transcription 1 (STAT1), an effector of interferon signaling, and of a set of downstream genes implicated in such signaling, was observed in the DNMT3B4 transfectants. There was significant correlation between the mRNA expression levels of DNMT3B4 and STAT1 in HCCs. mRNA expression levels of STAT1 and the three downstream genes examined were all significantly elevated in the chronic hepatitis and cirrhosis specimens compared with the normal liver specimens. Among the HCCs, the mRNA expression levels of STAT1 and the downstream genes were higher in tumors without portal vein involvement than in more malignant HCCs with portal vein involvement. Significant correlations between the mRNA expression levels of STAT1 and each of the downstream genes were observed in the tissue samples. Conclusions Overexpression of DNMT3B4 is involved in human hepatocarcinogenesis, even at the precancerous stages, not only by inducing chromosomal instability but also by affecting the expression of specific genes.
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Alterations in gene expression associated with the overexpression of a splice variant of DNA Methyltransferase 3B, DNMT3B4, during human hepatocarcinogenesis.
Journal of cancer research and clinical oncology, 2004Co-Authors: Yae Kanai, Yoshimasa Saito, Saori Ushijima, Setsuo HirohashiAbstract:Purpose Overexpression of a splice variant of DNA Methyltransferase 3B, DNMT3B4, correlates significantly with DNA hypomethylation in pericentromeric satellite regions, which is known to result in centromeric decondensation and enhanced chromosomal recombination in precancerous conditions and hepatocellular carcinomas (HCCs). We aimed to elucidate further the significance of DNMT3B4 during human hepatocarcinogenesis.
Xiao-yan Wang - One of the best experts on this subject based on the ideXlab platform.
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Single Nucleotide Polymorphism in DNMT3B Promoter and the Risk for Idiopathic Thrombocytopenic Purpura in Chinese Population
Journal of clinical immunology, 2008Co-Authors: Zhenping Chen, Zeping Zhou, Xiaoli Chen, Aijuan Liu, Zhen-xing Guo, Xiao-yan WangAbstract:Objective Epigenetic changes in gene expression, including DNA methylation and histone modifications, might contribute to autoimmunity. DNA methylation is mediated by a family of DNA Methyltransferases. Polymorphisms of the DNA Methyltransferase 3B (DNMT3B) gene may influence DNMT3B activity on DNA methylation, thereby modulating the susceptibility to some diseases. The purpose of this study was to investigate the association between the single nucleotide polymorphism (SNP) in promoter of the DNMT3B gene and the risk for development of idiopathic thrombocytopenic purpura (ITP).
Setsuo Hirohashi - One of the best experts on this subject based on the ideXlab platform.
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Alterations in gene expression associated with the overexpression of a splice variant of DNA Methyltransferase 3B, DNMT3B4, during human hepatocarcinogenesis
Journal of Cancer Research and Clinical Oncology, 2004Co-Authors: Yae Kanai, Yoshimasa Saito, Saori Ushijima, Setsuo HirohashiAbstract:Purpose Overexpression of a splice variant of DNA Methyltransferase 3B, DNMT3B4, correlates significantly with DNA hypomethylation in pericentromeric satellite regions, which is known to result in centromeric decondensation and enhanced chromosomal recombination in precancerous conditions and hepatocellular carcinomas (HCCs). We aimed to elucidate further the significance of DNMT3B4 during human hepatocarcinogenesis. Methods DNMT3B4-transfected human epithelial 293 cells were characterized using growth rate measurements, gene expression microarray, and quantitative reverse transcription-polymerase chain reaction (RT-PCR) analyses. RT-PCR was also performed on eight normal liver specimens, 45 noncancerous liver specimens showing chronic hepatitis or cirrhosis, which are considered to be precancerous conditions, and 56 HCCs. Results The growth rate of the DNMT3B4 transfectants was about double that of mock-transfectants. Induction of signal transducer and activator of transcription 1 (STAT1), an effector of interferon signaling, and of a set of downstream genes implicated in such signaling, was observed in the DNMT3B4 transfectants. There was significant correlation between the mRNA expression levels of DNMT3B4 and STAT1 in HCCs. mRNA expression levels of STAT1 and the three downstream genes examined were all significantly elevated in the chronic hepatitis and cirrhosis specimens compared with the normal liver specimens. Among the HCCs, the mRNA expression levels of STAT1 and the downstream genes were higher in tumors without portal vein involvement than in more malignant HCCs with portal vein involvement. Significant correlations between the mRNA expression levels of STAT1 and each of the downstream genes were observed in the tissue samples. Conclusions Overexpression of DNMT3B4 is involved in human hepatocarcinogenesis, even at the precancerous stages, not only by inducing chromosomal instability but also by affecting the expression of specific genes.
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Alterations in gene expression associated with the overexpression of a splice variant of DNA Methyltransferase 3B, DNMT3B4, during human hepatocarcinogenesis.
Journal of cancer research and clinical oncology, 2004Co-Authors: Yae Kanai, Yoshimasa Saito, Saori Ushijima, Setsuo HirohashiAbstract:Purpose Overexpression of a splice variant of DNA Methyltransferase 3B, DNMT3B4, correlates significantly with DNA hypomethylation in pericentromeric satellite regions, which is known to result in centromeric decondensation and enhanced chromosomal recombination in precancerous conditions and hepatocellular carcinomas (HCCs). We aimed to elucidate further the significance of DNMT3B4 during human hepatocarcinogenesis.
Zhujiang Zhao - One of the best experts on this subject based on the ideXlab platform.
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Expression pattern and clinical significance of DNA Methyltransferase 3B variants in gastric carcinoma.
Oncology reports, 2010Co-Authors: Fengchang Qiao, Xuemei Qiu, Wen-bin Huang, Zhujiang Zhao, Hong FanAbstract:The aim of this study was to detect the expression pattern of DNA Methyltransferase 3B (DNMT3B) variants in primary gastric cancer (GC) and to explore the clinical significance of DNMT3B variants in gastric carcinogenesis. Specific polymerase chain reaction (PCR) primer sets were designed to distinguish individual DNMT3B variants according to their splicing patterns. Expression levels of DNMT3B variants were assessed by quantitative real-time RT-PCR in gastric cancer tissue, normal gastric mucosae and GC cell lines. The relationship between the expression patterns of the DNMT3B variants and corresponding clinical information was analyzed by observing the expression levels of different variants in the tumors. These results demonstrate that DNMT3B overexpression is related to late phase invasion (P=0.029) and intestinal type (P=0.012) in GC. DNMT3B3 expression was higher in normal tissue, compared to tumor tissue (P=0.033). In contrast, only 18, 32 and 35% of the patient tumors overexpressed DNMT3B1, DNMT3B4 and DNMT3B5, respectively. While taking into account environmental factors (H. pylori, Epstein-Barr virus infection), H. pylori infection elevated DNMT3B1 and DNMT3B3 variants in tumors, while increasing DNMT3B4 in both tumor and non-cancerous tissues. Our findings indicated that the expression of DNMT3B3 is the major splice variant in normal gastric mucosae and may be affected by H. pylori infection. Elevated DNMT3B variants may influence the progression of gastric cancer and may possibly be a powerful indicator for the disease.
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Promoter polymorphisms of DNMT3B and the risk of colorectal cancer in Chinese: a case-control study
Journal of experimental & clinical cancer research : CR, 2008Co-Authors: Hong Fan, Feng Zhang, Dongsheng Liu, Zhujiang ZhaoAbstract:Background DNA-Methyltransferase-3B (DNMT3B), which plays a role in DNA methylation, is usually aberrant expression involved in carcinogenesis. Polymorphisms of the DNMT3B gene may influence DNMT3B activity on DNA methylation in several cancers, thereby modulating the susceptibility to cancer.
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Identification of potential genes regulated by DNA Methyltransferase 3B in a hepatocellular carcinoma cell line by RNA interference and microarray analysis.
Yi chuan xue bao = Acta genetica Sinica, 2005Co-Authors: Hong Fan, Zhujiang Zhao, Jianqiong Zhang, Wei XieAbstract:Whether DNA Methyltransferase 3B (DNMT3B) is deregulated in hepatocellular carcinoma cell lines is still unclear. The expression levels of DNMT3B protein in normal liver cell line, pericacinoma cell line and hepatocellular carcinoma cell lines were compared by both Western blotting and immunocytochemistry. Long-term downregulated DNMT3B in a hepatocellular carcinoma cell line SMMC-7721 was achieved using a RNAi recombinant plasmid. The suppression of DNMT3B induced by RNA interference was confirmed using semi-quantitative RT-PCR and Western blotting. High throughput cDNA microarray was used to analyze the expression profiling of downstream genes of DNMT3B displayed in the treated cell lines and control. In the result,DNMT3B in hepatocellular carcinoma cell lines was expressed at a significantly higher level compared to those in pericacinoma cell line and normal liver cell line. A specific DNMT3B siRNA stably expressed from a plasmid vector effectively suppressed the expression of DNMT3B in SMMC-7721 cell line. By microarray analysis,26 downregulated genes and 115 upregulated genes have been identified in the DNMT3B knockdown cell line,including some important developmental genes and tumor-related genes such as SNCG, NOTCH1, MBD3, WNT11, MAOA and FACL4. The discovery showed DNMT3B was over-expressed in most hepatocellular carcinoma cell lines examined and may be linked to the carcinogenesis of hepatocytes. An array of candidate genes that are involved in the action of DNMT3B have been identified,including those related to development.