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Transcriptional and post‐transcriptional control of DNA methyltransferase 3B is regulated by phosphatidylinositol 3 kinase/Akt pathway in human hepatocellular carcinoma cell lines
Author(s) -
Mei Chuanzhong,
Sun Lidong,
Liu Yonglei,
Yang Yong,
Cai Xiumei,
Liu Mingzhu,
Yao Wantong,
Wang Can,
Li Xin,
Wang Liying,
Li Zengxia,
Shi Yinghong,
Qiu Shuangjian,
Fan Jia,
Zha Xiliang
Publication year - 2010
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22684
Subject(s) - pi3k/akt/mtor pathway , protein kinase b , methyltransferase , ly294002 , transfection , biology , microbiology and biotechnology , dna methylation , cancer research , transcriptional regulation , methylation , chemistry , signal transduction , cell culture , gene expression , gene , biochemistry , genetics
DNA methyltransferases (DNMTs) are essential for maintenance of aberrant methylation in cancer cells and play important roles in the development of cancers. Unregulated activation of PI3K/Akt pathway is a prominent feature of many human cancers including human hepatocellular carcinoma (HCC). In present study, we found that DNMT3B mRNA and protein levels were decreased in a dose‐ and time‐dependent manner in HCC cell lines with LY294002 treatment. However, we detected that LY294002 treatment did not induce increase of the degradation of DNMT3B protein using protein decay assay. Moreover we found that Akt induced alteration of the expression of DNMT3B in cells transfected with myristylated variants of Akt2 or cells transfected with small interfering RNA respectively. Based on DNMT3B promoter dual‐luciferase reporter assay, we found PI3K pathway regulates DNMT3B expression at transcriptional level. And DNMT3B mRNA decay analysis suggested that down‐regulation of DNMT3B by LY294002 is also post‐transcriptional control. Furthermore, we demonstrated that LY294002 down‐regulated HuR expression in a time‐dependent manner in BEL‐7404. In summary, we have, for the first time, demonstrate that PI3K/Akt pathway regulates the expression of DNMT3B at transcriptional and post‐transcriptional levels, which is particularly important to understand the effects of PI3K/Akt and DNMT3B on hepatocarcinogenesis. J. Cell. Biochem. 111: 158–167, 2010. © 2010 Wiley‐Liss, Inc.