Epigenetic regulation of liver cancer stem cells and establishment of a novel therapeutic approach

肝癌干细胞的表观遗传调控及新治疗方法的建立

• 批准号: 23689039
• 负责人: CHIBA Tetsuhiro
• 金额: $ 16.31万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (A)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23689039/
• 关键词: エピジェネティクス; 肝癌; 肝臓; 幹細胞; 肝臓癌; 癌幹細胞; ポリコーム遺伝子; DZNep; 癌幹細胞特異的治療法

Polycomb group protein EZH2 is essential for the self-renewal of liver cancer stem cells. Short hairpin-RNA against EZH2 and 3-Deazaneplanocin A (DZNep) promotes the conversion toward differentiated progeny cells and reduced tumorigenic ability thorough the inhibition of H3K27 trimethylation (H3K27me3). We also conducted chromatin immunoprecipitation sequencing (ChIP-seq) analysis of normal hepatic stem cells using anti-H3K27me3 and anti-H3K4me3 antibodies, and successfully identified 562 bivalent genes. In combination with microarray data in the differentiation induction, candidate genes closely associated with hepatocytes and/or cholangiocytes were selected from bivalent genes. Since cancer-related genes were included among these genes, further analyses would be necessary to examine the role of these molecules in normal hepatic stem cells and liver cancer stem cells.

多梳族蛋白EZH 2对肝癌干细胞的自我更新至关重要针对EZH 2和3-去氮Planocin A（DZNep）的短发夹-RNA通过抑制H3 K27三甲基化（H3 K27 me 3）促进向分化的子代细胞的转化和降低的致瘤能力。我们还使用抗H3 K27 me 3和抗H3 K4 me 3抗体对正常肝干细胞进行了染色质免疫沉淀测序（ChIP-seq）分析，并成功鉴定了562个二价基因。结合微阵列数据，从二价基因中筛选出与肝细胞和/或胆管细胞密切相关的候选基因。由于这些基因中包括癌症相关基因，因此有必要进一步分析这些分子在正常肝干细胞和肝癌干细胞中的作用。

项目成果

Natural history of postvascular-phase iso-enhanced lesions on the sonogram in chronic liver diseases

慢性肝病超声图像上血管后期等增强病变的自然史

• DOI: 10.1111/jgh.12449
• 发表时间: 2014
• 期刊: J Gastroenterol Hepatol
• 作者: Kondo T;Maruyama H;Sekimoto T;Shimada T;Takahashi M;Chiba T;Kanai F;Yokosuka O;Yamaguchi T
• 通讯作者: Yamaguchi T

Prognosis of the hepatic nodules that show hypovascular in arterial phase and hypointense in hepatobiliary phase on gadoxetic acid enhanced MRI

钆塞酸增强MRI显示动脉期血供不足、肝胆期低信号的肝结节的预后

• 发表时间: 2013
• 作者: Ooka Y;Kanai F;Motoyama T;Ogasawara S;Suzuki E;Tawada A;Chiba T;Yokosuka O
• 通讯作者: Yokosuka O

幹細胞マーカーアルデヒド脱水素酵素1(ALDH1)の肝癌における解析

肝癌干细胞标志物乙醛脱氢酶 1 (ALDH1) 分析

• 发表时间: 2012
• 作者: 鈴木英一郎;千葉哲博;横須賀收
• 通讯作者: 横須賀收

肝癌幹細胞に対するエピジェネティック治療の可能性

肝癌干细胞表观遗传学治疗的可能性

• 发表时间: 2011
• 作者: 千葉哲博;ら
• 通讯作者: ら

肝癌幹細胞治療薬としてのジスルフィラムの有用性の検証

验证双硫仑作为肝癌干细胞治疗药物的有效性

• 作者: 鈴木英一郎;千葉哲博;金井文彦;斉藤朋子;叶川直哉;元山天佑;小笠原定久;大岡美彦;太和田暁之;岩間厚志;横須賀收
• 通讯作者: 横須賀收