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KAKEN_24590993seika.pdf
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Download
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:342.4 KB
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:Apr 11, 2016 |
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Total downloads since Apr 11, 2016 : 1006
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| Title |
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肝癌におけるエピゲノム変化の解析とヒストンアセチル化を標的とした新規治療の探索
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カンガン ニ オケル エピゲノム ヘンカ ノ カイセキ ト ヒストンアセチルカ オ ヒョウテキ ト シタ シンキ チリョウ ノ タンサク
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Kangan ni okeru epigenomu henka no kaiseki to hisutonasechiruka o hyoteki to shita shinki chiryo no tansaku
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Analysis of epigenetic changes in hepatocellular carcinoma and an investigation for a new therapeutic modality targeting histone acetylation
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齋藤, 英胤
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サイトウ, ヒデツグ
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Saito, Hidetsugu
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慶應義塾大学・薬学部・教授
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Research team head
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科研費研究者番号 : 80186949
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増野, 匡彦
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マシノ, タダヒコ
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Mashino, Tadahiko
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慶應義塾大学・薬学部・教授
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Research team member
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科研費研究者番号 : 90165697
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齋藤, 義正
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サイトウ, ヨシマサ
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Saito, Yoshimasa
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慶應義塾大学・薬学部・准教授
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Research team member
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科研費研究者番号 : 90360114
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2015
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科学研究費補助金研究成果報告書
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2014
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| Abstract |
肝細胞癌及びウイルス感染を含むその原因に対する新たな治療としてエピゲノム変化のうちヒストン修飾変化の可能性を探索することを目的とした。C型肝炎ウイルス(HCV)を感染した肝癌細胞株に対して, ヒストン脱アセチル化酵素阻害薬(HDACi)SAHAは, 宿主細胞遺伝子発現変化を介してHCV増殖抑制効果を示し, EZH2の阻害作用により細胞増殖を抑制するものと考えられた。HCV持続感染にはNrf2遺伝子発現が重要で, HCVや細胞増殖にはNrf2, EZH2, miR-122の相互作用により影響されることが示唆された。
The aim of this study was to investigate a new therapeutic strategy against hepatocellular carcinoma (HCC) and viral infection using epigenetic changes especially by the histone modifier. Cell lines infected with hepatitis C virus (HCV) or replicons were used in this study. Histone deacetylase inhibitor (HDACi), SAHA, inhibited HCV replication by changing host cellular gene expressions as well as decreasing cellular proliferation by inhibiting EZH2 expression. Nrf2 expression was important for long-term HCV infection in the cell line, and expression levels of Nrf2, EZH2 and miR-122 mutually affect proliferation of cells and also HCV.
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研究種目 : 基盤研究(C)
研究期間 : 2012～2014
課題番号 : 24590993
研究分野 : 消化器内科学
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