| Project/Area Number |
24592033
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
BEPPU Toru 熊本大学, 医学部附属病院, 特任教授 (70301372)
OKABE Hirohisa 熊本大学, 医学部附属病院, 特任助教 (40573621)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Enhancer / cholangiocarcinoma / epigenetics / cell cycle / apoptosis / p16INK4A / p27KIP1 / 3-deazaneplanocin A / Zeste Homolog 2 / Cholangiocarcinoma / gemcitabine / EZH2 / ポリコーム蛋白 / 胆管癌 / 細胞周期 / アポトーシス / DZNep |
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| Outline of Final Research Achievements |
In Intra- and extra-hepatic cholangiocarcinoma patients, EZH2 high expression was significantly correlated with the poor prognosis by using immunohistochemical analysis. In vitro analysis, knockdown of EZH2 reduced cell growth and induced G1 arrest, and induced apoptosis. Moreover, a knockdown of EZH2 increased the expression of p16INK4A and p27KIP1 in real time PCR. An EZH2 inhibitor, DZNep reduce the expression of EZH2 and demethylase H3K27, and result to reduce cell proliferation. Inhibition of EZH2 by DZNep also induced G1 arrest and induced apoptosis, and increased the expression of p16INK4A and p27KIP1 which revealed by western blotting. As conclusion, this study demonstrates that the high expression of EZH2 accelerate tumor malignancy and is related to poor prognosis in patients with cholangiocarcinoma. Pharmacological inhibition of EZH2 by DZNep can also inhibit cell proliferation. These results suggest that EZH2 is a potential therapeutic target for cholangiocarcinoma.
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