Role of promoter methylation in increased methionine adenosyltransferase 2A expression in human liver cancer

2001 ◽  
Vol 280 (2) ◽  
pp. G184-G190 ◽  
Author(s):  
Heping Yang ◽  
Zong-Zhi Huang ◽  
Zhaohui Zeng ◽  
Changjin Chen ◽  
Robert R. Selby ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Promoter Methylation ◽  
Human Liver ◽  
Trichostatin A ◽  
Normal Liver ◽  
Methionine Adenosyltransferase ◽  
Endogenous Expression ◽  
Human Liver Cancer

Methionine adenosyltransferase (MAT), an essential enzyme that catalyzes the formation of S-adenosylmethionine (SAM), is encoded by two genes, MAT1A (liver-specific) and MAT2A (non-liver-specific). We showed a switch from MAT1A to MAT2A expression in human liver cancer, which facilitates cancer cell growth. The present work examined the role of methylation in MAT2A transcriptional regulation. We found that the human MAT2A promoter is hypomethylated in hepatocellular carcinoma, in which the gene is upregulated transcriptionally, but hypermethylated in normal liver, in which the gene is minimally expressed. Luciferase activities driven by in vitro methylated MAT2A promoter constructs were 75–95% lower than activities driven by unmethylated constructs. SAM treatment of Hep G2 cells reduced MAT2A endogenous expression by 75%, hypermethylated the MAT2A promoter, and reduced luciferase activities driven by MAT2A promoter constructs by 65–75% while not affecting MAT1A's promoter activity. Treatment of adult rat and human hepatocytes with trichostatin A, an inhibitor of histone deacetylase, upregulated MAT2Aexpression by more than fourfold. Collectively, these results suggest that MAT2A expression is regulated by promoter methylation and histone acetylation.

scholarly journals Leptin's mitogenic effect in human liver cancer cells requires induction of both methionine adenosyltransferase 2A and 2β

Hepatology ◽  
2007 ◽  
Vol 47 (2) ◽  
pp. 521-531 ◽  
Author(s):  
Komal Ramani ◽  
Heping Yang ◽  
Meng Xia ◽  
Ainhoa Iglesias Ara ◽  
José M. Mato ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Human Liver ◽  
Methionine Adenosyltransferase ◽  
Mitogenic Effect ◽  
Liver Cancer Cells ◽  
Human Liver Cancer ◽  
Human Liver Cancer Cells

The interaction of bacterial magnetosomes and human liver cancer cells in vitro

2017 ◽  
Vol 427 ◽  
pp. 105-110 ◽  
Author(s):  
Pingping Wang ◽  
Chuanfang Chen ◽  
Changyou Chen ◽  
Yue Li ◽  
Weidong Pan ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Human Liver ◽  
Liver Cancer Cells ◽  
Human Liver Cancer ◽  
Human Liver Cancer Cells

scholarly journals Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines In Vitro and In Vivo

2019 ◽  
Vol 39 (11) ◽  
pp. 5973-5982 ◽  
Author(s):  
SACHIKO OGASAWARA ◽  
YUTARO MIHARA ◽  
REIICHIRO KONDO ◽  
HIRONORI KUSANO ◽  
JUN AKIBA ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Liver ◽  
Antiproliferative Effect ◽  
Liver Cancer Cell ◽  
Human Liver Cancer Cell ◽  
Human Liver Cancer

scholarly journals In vivo and in vitro inhibition of human liver cancer progress by downregulation of the μ-opioid receptor and relevant mechanisms

2013 ◽  
Vol 30 (4) ◽  
pp. 1731-1738 ◽  
Author(s):  
JIN LU ◽  
ZEFENG LIU ◽  
LINGLING ZHAO ◽  
HUIMIN TIAN ◽  
XIUHUA LIU ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Opioid Receptor ◽  
Human Liver ◽  
Human Liver Cancer ◽  
Μ Opioid Receptor ◽  
In Vitro Inhibition

scholarly journals Hepatocarcinogenesis in FXR−/− Mice Mimics Human HCC Progression That Operates through HNF1α Regulation of FXR Expression

2012 ◽  
Vol 26 (5) ◽  
pp. 775-785 ◽  
Author(s):  
Nian Liu ◽  
Zhipeng Meng ◽  
Guiyu Lou ◽  
Weiping Zhou ◽  
Xiaoqiong Wang ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Human Liver ◽  
Gene Promoter ◽  
Normal Liver ◽  
Nuclear Hormone Receptor ◽  
Farnesoid X Receptor ◽  
Gene Profiling ◽  
Wild Type ◽  
Human Liver Cancer ◽  
Liver Tissues

Abstract Farnesoid X receptor (FXR) (nuclear receptor subfamily 1, group H, member 4) is a member of nuclear hormone receptor superfamily, which plays essential roles in metabolism of bile acids, lipid, and glucose. We previously showed spontaneously hepatocarcinogenesis in aged FXR−/− mice, but its relevance to human hepatocellular carcinoma (HCC) is unclear. Here, we report a systematical analysis of hepatocarcinogenesis in FXR−/− mice and FXR expression in human liver cancer. In this study, liver tissues obtained from FXR−/− and wild-type mice at different ages were compared by microarray gene profiling, histological staining, chemical analysis, and quantitative real-time PCR. Primary hepatic stellate cells and primary hepatocytes isolated from FXR−/− and wild-type mice were also analyzed and compared. The results showed that the altered genes in FXR−/− livers were mainly related to metabolism, inflammation, and fibrosis, which suggest that hepatocarcinogenesis in FXR−/− mice recapitulated the progression of human liver cancer. Indeed, FXR expression in human HCC was down-regulated compared with normal liver tissues. Furthermore, the proinflammatory cytokines, which were up-regulated in human HCC microenvironment, decreased FXR expression by inhibiting the transactivity of hepatic nuclear factor 1α on FXR gene promoter. Our study thereby demonstrates that the down-regulation of FXR has an important role in human hepatocarcinogenesis and FXR−/− mice provide a unique animal model for HCC study.

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