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首页> 外文期刊>Radiotherapy and oncology: Journal of the European Society for Therapeutic Radiology and Oncology >Translational control is a major contributor to hypoxia induced gene expression.
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Translational control is a major contributor to hypoxia induced gene expression.

机译：翻译控制是低氧诱导的基因表达的主要贡献者。

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BACKGROUND AND PURPOSE: Hypoxia is a common feature of solid tumors that is associated with an aggressive phenotype, resistance to therapy and poor prognosis. Major contributors to these adverse effects are the transcriptional program activated by the HIF family of transcription factors as well as the translational response mediated by PERK-dependent phosphorylation of eIF2alpha and inhibition of mTORC1 activity. In this study we determined the relative contribution of both transcriptional and translational responses to changes in hypoxia induced gene expression. MATERIAL AND METHODS: Total and efficiently translated (polysomal) mRNA was isolated from DU145 prostate carcinoma cells that were exposed for up to 24 h of hypoxia (<0.02% O(2)). Changes in transcription and translation were assessed using affymetrix microarray technology. RESULTS: Our data reveal an unexpectedly large contribution of translation control on both induced and repressed gene expression at all hypoxic time points, particularly during acute hypoxia (2-4 h). Gene ontology analysis revealed that gene classes like transcription and signal transduction are stimulated by translational control whereas expression of genes involved in cell growth and protein metabolism are repressed during hypoxic conditions by translational control. CONCLUSIONS: Our data indicate that translation influences gene expression during hypoxia on a scale comparable to that of transcription.
机译：背景与目的：缺氧是实体瘤的常见特征，与侵袭性表型，对治疗的抵抗力和不良预后有关。这些不良反应的主要起因是转录因子的HIF家族激活的转录程序，以及eIF2alpha的PERK依赖性磷酸化和mTORC1活性抑制介导的翻译反应。在这项研究中，我们确定了转录和翻译反应对缺氧诱导的基因表达变化的相对贡献。材料与方法：总和有效翻译的（多体性）mRNA从暴露于缺氧长达24小时（<0.02％O（2））的DU145前列腺癌细胞中分离出来。使用affymetrix微阵列技术评估转录和翻译的变化。结果：我们的数据显示在所有缺氧时间点，特别是在急性缺氧（2-4小时）期间，翻译控制对诱导和抑制的基因表达均具有意想不到的巨大贡献。基因本体分析表明，翻译控制可刺激转录和信号转导等基因类别，而低氧条件下通过翻译控制可抑制涉及细胞生长和蛋白质代谢的基因表达。结论：我们的数据表明，在缺氧状态下翻译影响基因表达的程度与转录相当。

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