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Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Apr 28, 2009; 15(16): 2020-2026
Published online Apr 28, 2009. doi: 10.3748/wjg.15.2020
Overexpression of DNA methyltransferase 1 and its biological significance in primary hepatocellular carcinoma
Hong Fan, Zhu-Jiang Zhao, Jian Cheng, Xian-Wei Su, Qing-Xiang Wu, Yun-Feng Shan
Hong Fan, Zhu-Jiang Zhao, Xian-Wei Su, Qing-Xiang Wu, 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
Jian Cheng, Prenatal Diagnosis Center, Nanjing maternity and Child Health Care Hospital, Nanjing 210004, Jiangsu Province, China
Yun-Feng Shan, Key Lab of Enteric Pathogenic Microbiology Ministry of Health, Jiangsu Centers for Diseases Prevention and Control, Nanjing 210009, Jiangsu Province, China
Author contributions: Fan H, Zhao ZJ performed the majority of experiments; Cheng J and Wu QX helped to perform the IHC; Su XW performed the statistical analysis of case information; Shan YF did experiments on cultured cell lines; Fan H designed the study and wrote the manuscript.
Correspondence to: Hong Fan, PhD, Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University, Nanjing 210009, Jiangsu Province, China.
Telephone: +86-25-83272314
Fax: +86-25-84463798
Received: January 4, 2009
Revised: February 23, 2009
Accepted: March 2, 2009
Published online: April 28, 2009

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 significantly 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 significant 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 findings implied that DNMT1 plays a key role in HBV-related hepatocellular tumorigenesis. Depletion of DNMT1 mediates growth suppression in SMMC-7721 cells.

Keywords: DNA methyltransferase 1, Hepatitis B virus-related hepatocellular carcinoma, RNAi, Cell proliferation, Apoptosis