Hypoxia-inducible mir-210 regulates normoxic gene expression involved in tumor initiation.
Hypoxia-inducible mir-210 regulates normoxic gene expression involved in tumor initiation.
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DOI：
10.1016/j.molcel.2009.09.006
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发表时间：
2009-09-24
期刊：
影响因子：
16
通讯作者：
Giaccia, Amato J.
中科院分区：
文献类型：
--
作者：
Huang, Xin;Ding, Lianghao;Bennewith, Kevin L.;Tong, Ricky T.;Welford, Scott M.;Ang, K. Kian;Story, Michael;Le, Quynh-Thu;Giaccia, Amato J.
以往的研究表明，HIF转录因子可以激活和抑制基因表达。在这里，我们表明，HIF 1通过缺氧反应元件调节mir-210在各种肿瘤类型中的表达。在原发性头颈部肿瘤样品中的表达分析表明，mir-210可以作为肿瘤缺氧的体内标志物。通过Argonaute蛋白免疫沉淀，我们确定了50个潜在的mir-210靶点，并验证了随机选择的。这50个基因中的大多数不是经典的低氧诱导基因，表明mir-210抑制在常氧下表达的基因，这些基因不再是适应低氧环境和在低氧环境中生存所必需的。当异位表达mir-210的人头颈部或胰腺肿瘤细胞植入免疫缺陷小鼠时，mir-210抑制肿瘤生长的起始。综上所述，这些数据暗示了mir-210在调节肿瘤细胞的缺氧反应和肿瘤生长中的重要作用。
Previous studies have suggested that the HIF transcription factors can both activate and inhibit gene expression. Here we show that HIF1 regulates the expression of mir-210 in a variety of tumor types through a hypoxia responsive element. Expression analysis in primary head & neck tumor samples indicates that mir-210 may serve as an in vivo marker for tumor hypoxia. By Argonaute protein immunoprecipitation, we identified 50 potential mir-210 targets and validated randomly selected ones. The majority of these 50 genes are not classical hypoxia inducible genes, suggesting mir-210 represses genes expressed under normoxia that are no longer necessary to adapt and survive in a hypoxic environment. When human head and neck or pancreatic tumor cells ectopically expressing mir-210 were implanted into immunodeficient mice, mir-210 repressed initiation of tumor growth. Taken together, these data implicate an important role for mir-210 in regulating the hypoxic response of tumor cells and tumor growth.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
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影响因子：
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作者：
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