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


CONCLUSIONS
The findings implied that DNMT1 plays a key role in HBV-related hepatocellular tumorigenesis. Depletion of DNMT1 mediates growth suppression in SMMC-7721 cells.
Fan
Hong
H
Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University, Nanjing, Jiangsu Province, China. fanh@seu.edu.cn
Zhao
Zhu-Jiang
ZJ
Cheng
Jian
J
Su
Xian-Wei
XW
Wu
Qing-Xiang
QX
Shan
Yun-Feng
YF
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D034622:RNA Interference
D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human