Depletion of DNMT3A Suppressed Cell Proliferation and Restored PTEN in Hepatocellular Carcinoma Cell
Promoter hypermethylation mediated by DNA methyltransferases (DNMTs) is the main reason for epigenetic inactivation of tumor suppressor genes (TSGs). Previous studies showed that DNMT1 and DNMT3B play an important role in CpG island methylation in tumorigenesis. Little is known about the role of DNM...
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doaj-1e4f308e52b14f9bad01ddd7ddc8e8c22020-11-25T01:33:16ZengHindawi LimitedJournal of Biomedicine and Biotechnology1110-72431110-72512010-01-01201010.1155/2010/737535737535Depletion of DNMT3A Suppressed Cell Proliferation and Restored PTEN in Hepatocellular Carcinoma CellZhujiang Zhao0Qingxiang Wu1Jian Cheng2Xuemei Qiu3Jianqiong Zhang4Hong Fan5Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University, Nanjing 210009, ChinaKey Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University, Nanjing 210009, ChinaPrenatal Diagnosis Center, Nanjing Maternity and Child Health Care Hospital, Nanjing 210009, ChinaKey Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University, Nanjing 210009, ChinaKey Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University, Nanjing 210009, ChinaKey Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University, Nanjing 210009, ChinaPromoter hypermethylation mediated by DNA methyltransferases (DNMTs) is the main reason for epigenetic inactivation of tumor suppressor genes (TSGs). Previous studies showed that DNMT1 and DNMT3B play an important role in CpG island methylation in tumorigenesis. Little is known about the role of DNMT3A in this process, especially in hepatocellular carcinoma (HCC). In the present study, increased DNMT3A expression in 3 out of 6 HCC cell lines and 16/25 (64%) HCC tissues implied that DNMT3A is involved in hepatocellular carcinogenesis. Depletion of DNMT3A in HCC cell line SMMC-7721 inhibited cell proliferation and decreased the colony formation (about 65%). Microarray data revealed that 153 genes were upregulated in DNMT3A knockdown cells and that almost 71% (109/153) of them contain CpG islands in their 5′ region. 13 of them including PTEN, a crucial tumor suppressor gene in HCC, are genes involved in cell cycle and cell proliferation. Demethylation of PTEN promoter was observed in DNMT3A-depleted cells implying that DNMT3A silenced PTEN via DNA methylation. These results provide insights into the mechanisms of DNMT3A to regulate TSGs by an epigenetic approach in HCC.http://dx.doi.org/10.1155/2010/737535 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhujiang Zhao Qingxiang Wu Jian Cheng Xuemei Qiu Jianqiong Zhang Hong Fan |
spellingShingle |
Zhujiang Zhao Qingxiang Wu Jian Cheng Xuemei Qiu Jianqiong Zhang Hong Fan Depletion of DNMT3A Suppressed Cell Proliferation and Restored PTEN in Hepatocellular Carcinoma Cell Journal of Biomedicine and Biotechnology |
author_facet |
Zhujiang Zhao Qingxiang Wu Jian Cheng Xuemei Qiu Jianqiong Zhang Hong Fan |
author_sort |
Zhujiang Zhao |
title |
Depletion of DNMT3A Suppressed Cell Proliferation and Restored PTEN in Hepatocellular Carcinoma Cell |
title_short |
Depletion of DNMT3A Suppressed Cell Proliferation and Restored PTEN in Hepatocellular Carcinoma Cell |
title_full |
Depletion of DNMT3A Suppressed Cell Proliferation and Restored PTEN in Hepatocellular Carcinoma Cell |
title_fullStr |
Depletion of DNMT3A Suppressed Cell Proliferation and Restored PTEN in Hepatocellular Carcinoma Cell |
title_full_unstemmed |
Depletion of DNMT3A Suppressed Cell Proliferation and Restored PTEN in Hepatocellular Carcinoma Cell |
title_sort |
depletion of dnmt3a suppressed cell proliferation and restored pten in hepatocellular carcinoma cell |
publisher |
Hindawi Limited |
series |
Journal of Biomedicine and Biotechnology |
issn |
1110-7243 1110-7251 |
publishDate |
2010-01-01 |
description |
Promoter hypermethylation mediated by DNA methyltransferases (DNMTs) is the main reason for epigenetic inactivation of tumor suppressor genes (TSGs). Previous studies showed that DNMT1 and DNMT3B play an important role in CpG island methylation in tumorigenesis. Little is known about the role of DNMT3A in this process, especially in hepatocellular carcinoma (HCC). In the present study, increased DNMT3A expression in 3 out of 6 HCC cell lines and 16/25 (64%) HCC tissues implied that DNMT3A is involved in hepatocellular carcinogenesis. Depletion of DNMT3A in HCC cell line SMMC-7721 inhibited cell proliferation and decreased the colony formation (about 65%). Microarray data revealed that 153 genes were upregulated in DNMT3A knockdown cells and that almost 71% (109/153) of them contain CpG islands in their 5′ region. 13 of them including PTEN, a crucial tumor suppressor gene in HCC, are genes involved in cell cycle and cell proliferation. Demethylation of PTEN promoter was observed in DNMT3A-depleted cells implying that DNMT3A silenced PTEN via DNA methylation. These results provide insights into the mechanisms of DNMT3A to regulate TSGs by an epigenetic approach in HCC. |
url |
http://dx.doi.org/10.1155/2010/737535 |
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