The roles of HIF-DEC pathway on DNA repair systems in hypoxic oral cancer cells.

HIF-DEC 通路对缺氧口腔癌细胞 DNA 修复系统的作用。

• 批准号: 23592766
• 负责人: TANIMOTO Keiji
• 金额: $ 3.24万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592766/
• 关键词: Hypoxia; HIF; DEC; DNA repair; Transcription; Cancer cells; Cancer cell

In this study, we analyzed expression changes of numerous DNA repair-related genes under hypoxia, further noted that the effect of the changes to radiation sensitivities. Comprehensive gene expression analyses showed that 50 of 130 DNA repair-related genes were included in down-regulated genes under hypoxia. Among these genes we selected 6 genes and confirmed quantitative decreased expressions. Co-transfection reporter assay elucidated that DEC1 or DEC2 repressed those DNA repair-related genes promoter activities. In addition, knockdown of HIF1A or DEC2 attenuated hypoxic suppression of DNA repair-related gene expressions. Interestingly, detection and repair of DNA double-strand breaks by irradiations were inhibited in hypoxic pre-incubated cells. Moreover, knockdown of DEC2 increased radiation sensitivities in those cells. These data suggested that HIF-1-DEC pathway especially DEC2 play a pivotal role in radiation sensitivity via suppression of DNA repair gene expressions.

本研究分析了低氧条件下DNA修复相关基因的表达变化，进一步观察了低氧对辐射敏感性的影响。综合基因表达分析表明，在130个DNA修复相关基因中，有50个基因在缺氧条件下表达下调。在这些基因中，我们选择了6个基因，并证实了定量表达下降。共转染报告基因实验证实DEC 1或DEC 2抑制了DNA修复相关基因的启动子活性。此外，HIF 1A或DEC 2的敲低减弱了DNA修复相关基因表达的缺氧抑制。有趣的是，检测和修复的DNA双链断裂的辐射抑制缺氧预孵育的细胞。此外，DEC 2的敲低增加了这些细胞的辐射敏感性。提示HIF-1-DEC通路尤其是DEC 2通过抑制DNA修复基因的表达在辐射敏感性中起重要作用。

项目成果

A Step forward into respiratory genetics : Overview contribution of genetics in respiratory diseases

呼吸遗传学的进步：遗传学在呼吸系统疾病中的概述贡献

• 发表时间: 2012
• 期刊: Asian Biomedicine
• 影响因子: 0.6
• 作者: Andika C. Putra;Keiji Tanimoto;Elisna Syahruddin;Sita Andarini;Yoshio Hosoi;Keiko Hiyama
• 通讯作者: Keiko Hiyama

Yoshio Hosoi. Mitochondria are required for ATM activation by extranuclear oxidative stress in cultured human hepatoblastoma cell line Hep G2 cells

细井义夫.

• 发表时间: 2013
• 期刊: Biochemical and Biophysical Research Communications
• 影响因子: 3.1
• 作者: Akinori Morita;Keiji Tanimoto;Tomoki Murakami;Takeshi Morinaga;Yoshio Hosoi
• 通讯作者: Yoshio Hosoi

がん細胞における低酸素応答機構の解明

阐明癌细胞的缺氧反应机制

• 发表时间: 2012
• 作者: 角美佐;市川陽子;高木幸則;榮田智;木村泰男;佐々木美穂;中村卓;谷本圭司
• 通讯作者: 谷本圭司

TMEM158 and FBLP1 as novel marker genes of cisplatin sensitivity in non-small cell lung cancer cells

• DOI: 10.3109/01902148.2012.731625
• 发表时间: 2012-11-01
• 期刊: EXPERIMENTAL LUNG RESEARCH
• 影响因子: 1.7
• 作者: Mohammed, Ahmed El Sayed;Eguchi, Hidetaka;Nishiyama, Masahiko
• 通讯作者: Nishiyama, Masahiko

低酸素研究の10年−低酸素応答のゲノム研究−

缺氧研究10年-缺氧反应的基因组研究-

• 发表时间: 2012
• 作者: Sato Eida;Marc Van Cauteren;Yuka Hotokezaka;Makoto Obara;Tomoaki Okuaki;Ikuo Katayama;Miho Sasaki;Misa Sumi;and Takashi Nakamura;森崎市治郎ほか;谷本圭司
• 通讯作者: 谷本圭司