Promoter hypermethylation mediated downregulation of FBP1 in human hepatocellular carcinoma and colon cancer.
Promoter hypermethylation mediated downregulation of FBP1 in human hepatocellular carcinoma and colon cancer.
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DOI：
10.1371/journal.pone.0025564
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Shi G
中科院分区：
文献类型：
--
作者：
Chen M;Zhang J;Li N;Qian Z;Zhu M;Li Q;Zheng J;Wang X;Shi G
FBP1，果糖-1,6-二磷酸酶-1，是一种糖异生调节酶，催化果糖1,6-二磷酸水解为果糖6-磷酸和无机磷酸。它在胃癌中拮抗糖酵解并通过NF-kappaB途径被表观遗传失活的机制已被报道。然而，其在肝癌发生中的作用尚不清楚。在这里，我们研究了FBP1在原发性HCC和结肠肿瘤中的表达和DNA甲基化。FBP1在80%（8/10）的人肝癌细胞系、66.7%（6/9）的肝癌细胞系和100%（6/6）的结肠癌细胞系中低表达，但在配对的邻近非肿瘤组织和永生化正常细胞系中表达较高，这与其启动子甲基化状态密切相关。在原发性hcc、胃和结肠肿瘤组织中进一步检测到甲基化，但在成对的邻近非肿瘤组织中没有或偶尔检测到甲基化。亚硫酸氢盐基因组测序对327bp启动子区域29个CpG位点进行了详细的甲基化分析，证实了其甲基化。FBP1沉默可以通过5-aza-2 ' -脱氧胞苷（Aza）的化学去甲基化处理逆转，表明直接的表观遗传沉默。恢复低表达细胞中FBP1的表达，通过诱导G2-M期细胞周期阻滞，显著抑制细胞生长和集落形成能力。此外，观察到的效果与活性氧（ROS）生成的增加相一致。综上所述，FBP1的表观遗传失活在人类肝癌和结肠癌中也很常见。FBP1似乎是一种功能性肿瘤抑制因子，参与肝脏和结肠癌的发生。
FBP1, fructose-1,6-bisphosphatase-1, a gluconeogenesis regulatory enzyme, catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate. The mechanism that it functions to antagonize glycolysis and was epigenetically inactivated through NF-kappaB pathway in gastric cancer has been reported. However, its role in the liver carcinogenesis still remains unknown. Here, we investigated the expression and DNA methylation of FBP1 in primary HCC and colon tumor. FBP1 was lowly expressed in 80% (8/10) human hepatocellular carcinoma, 66.7% (6/9) liver cancer cell lines and 100% (6/6) colon cancer cell lines, but was higher in paired adjacent non-tumor tissues and immortalized normal cell lines, which was well correlated with its promoter methylation status. Methylation was further detected in primary HCCs, gastric and colon tumor tissues, but none or occasionally in paired adjacent non-tumor tissues. Detailed methylation analysis of 29 CpG sites at a 327-bp promoter region by bisulfite genomic sequencing confirmed its methylation. FBP1 silencing could be reversed by chemical demethylation treatment with 5-aza-2′-deoxycytidine (Aza), indicating direct epigenetic silencing. Restoring FBP1 expression in low expressed cells significantly inhibited cell growth and colony formation ability through the induction of G2-M phase cell cycle arrest. Moreover, the observed effects coincided with an increase in reactive oxygen species (ROS) generation. In summary, epigenetic inactivation of FBP1 is also common in human liver and colon cancer. FBP1 appears to be a functional tumor suppressor involved in the liver and colon carcinogenesis.
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影响因子：
6.4
作者：
Berndtsson, Maria;Hagg, Maria;Linder, Stig
通讯作者：
Linder, Stig
DOI：
10.1007/978-1-60761-411-1_4
发表时间：
2010-01-01
期刊：
ADVANCED PROTOCOLS IN OXIDATIVE STRESS II
影响因子：
--
作者：
Eruslanov, Evgeniy;Kusmartsev, Sergei
通讯作者：
Kusmartsev, Sergei
DOI：
10.1016/j.bbrc.2008.10.045
发表时间：
2008-12-12
影响因子：
3.1
作者：
Bigl, Marina;Jandrig, Burkhard;Eschrich, Klaus
通讯作者：
Eschrich, Klaus
影响因子：
11.5
作者：
Fruehauf, John P.;Meyskens, Frank L., Jr.
通讯作者：
Meyskens, Frank L., Jr.
DOI：
10.1042/bj20081258
发表时间：
2009-02-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Aykin-Burns N;Ahmad IM;Zhu Y;Oberley LW;Spitz DR
通讯作者：
Spitz DR