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Promoter hypermethylation mediated downregulation of FBP1 in human hepatocellular carcinoma and colon cancer.

Chen M, Zhang J, Li N, Qian Z, Zhu M, Li Q, Zheng J, Wang X, Shi G - PLoS ONE (2011)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.

ABSTRACT
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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Effect of FBP1 on the cell cycle of liver and colon cancer cell line.The cell cycle distribution of liver and colon cancer cell line (SW480 and SMMC-7721) with and without FBP1 expression was evaluated by flow cytometry analysis. (A) and (B) Representative fluorescence -activated cell sorting analysis of cancer cells transfected with or without FBP1.
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pone-0025564-g005: Effect of FBP1 on the cell cycle of liver and colon cancer cell line.The cell cycle distribution of liver and colon cancer cell line (SW480 and SMMC-7721) with and without FBP1 expression was evaluated by flow cytometry analysis. (A) and (B) Representative fluorescence -activated cell sorting analysis of cancer cells transfected with or without FBP1.

Mentions: To determine the molecular mechanism by which FBP1 suppressed colony formation and cell proliferation, we investigated the effect of FBP1 on cell cycle distribution. After propidium iodide staining, fluorescence-activated cell sorting analysis of FBP1 overexpressed SW480 and SMMC-7721 cells revealed an increase in the number of G2-M phase cells and a decrease in the number of S phase cells (Figure 5A and 5B).


Promoter hypermethylation mediated downregulation of FBP1 in human hepatocellular carcinoma and colon cancer.

Chen M, Zhang J, Li N, Qian Z, Zhu M, Li Q, Zheng J, Wang X, Shi G - PLoS ONE (2011)

Effect of FBP1 on the cell cycle of liver and colon cancer cell line.The cell cycle distribution of liver and colon cancer cell line (SW480 and SMMC-7721) with and without FBP1 expression was evaluated by flow cytometry analysis. (A) and (B) Representative fluorescence -activated cell sorting analysis of cancer cells transfected with or without FBP1.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198434&req=5

pone-0025564-g005: Effect of FBP1 on the cell cycle of liver and colon cancer cell line.The cell cycle distribution of liver and colon cancer cell line (SW480 and SMMC-7721) with and without FBP1 expression was evaluated by flow cytometry analysis. (A) and (B) Representative fluorescence -activated cell sorting analysis of cancer cells transfected with or without FBP1.
Mentions: To determine the molecular mechanism by which FBP1 suppressed colony formation and cell proliferation, we investigated the effect of FBP1 on cell cycle distribution. After propidium iodide staining, fluorescence-activated cell sorting analysis of FBP1 overexpressed SW480 and SMMC-7721 cells revealed an increase in the number of G2-M phase cells and a decrease in the number of S phase cells (Figure 5A and 5B).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus