Overexpression of DNA methyltransferase 1 and its biological significance in primary hepatocellular carcinoma

作     者：Hong Fan Zhu-Jiang Zhao Jian Cheng Xian-Wei Su Qing-Xiang Wu Yun-Feng Shan 

作者机构：Key Laboratory of Developmental Genes and Human Diseases Ministry of Education Southeast University Nanjing 210009 Jiangsu Province China Department of Genetics and Developmental Biology the School of Basic Medical Sciences Southeast University Nanjing 210009 Jiangsu Province China Prenatal Diagnosis Center Nanjing maternity and Child Health Care Hospital Nanjing 210004 Jiangsu Province China Key Lab of Enteric Pathogenic Microbiology Ministry of Health Jiangsu Centers for Diseases Prevention and Control Nanjing 210009 Jiangsu Province China 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2009年第15卷第16期

页      面：2020-2026页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：Supported by National Natural Science Foundation of China No.30470950 

主　　题：DNA甲基转移酶1 原发性肝癌 生物学意义 DNMT1 肝癌细胞株 免疫组织化学检查 乙型肝炎病毒 乙肝病毒阳性 

摘      要：AIM:To explore the relationship between DNA methyltransferase 1 (DNMT1) and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and its biological significance in primary HCC.METHODS: We carried out an immunohistochemical examination of DNMT1 in both HCC and paired non-neoplastic liver tissues from Chinese subjects. DNMT1 mRNA was further examined in HCC cell lines by real-time PCR. We inhibited DNMT1 using siRNA and detected the effect of depletion of DNMT1 on cell proliferation ability and cell apoptosis in the HCC cell line SMMC-7721.RESULTS: DNMT1 protein expression was increased in HCCs compared to histologically normal non-neoplastic liver tissues and the incidence of DNMT1 immunoreactivity in HCCs correlated signifi cantly with poor tumor differentiation (P=0.014). There were more cases with DNMT1 overexpression in HCC with HBV (42.85%) than in HCC without HBV (28.57%). However, no signif icant difference in DNMT1 expression was found in HBV-positive and HBV-negative cases in the Chinese HCC group. There was a trend that DNMT1 RNA expression increased more in HCC cell lines than in pericarcinoma cell lines and normal liver cell lines. In addition, we inhibited DNMT1 using siRNA in the SMMC-7721 HCC cell line and found depletion of DNMT1 suppressed cells growth independent of expression of proliferating cell nuclear antigen (PCNA), even in HCC cell lines where DNMT1 was stably decreased.CONCLUSION: The f indings implied that DNMT1 plays a key role in HBV-related hepatocellular tumorigenesis. Depletion of DNMT1 mediates growth suppression in SMMC-7721 cells.