MicroRNA-210: a unique and pleiotropic hypoxamir.
MicroRNA-210: a unique and pleiotropic hypoxamir.
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DOI：
10.4161/cc.9.6.11006
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发表时间：
2010-03-15
期刊：
影响因子：
--
通讯作者：
Loscalzo J
中科院分区：
文献类型：
--
作者：
Chan SY;Loscalzo J
氧气供应不足或缺氧会引发一系列复杂且尚未完全了解的适应性变化，这些变化影响细胞的存活和功能。其中许多适应性变化由一个主要的转录因子——缺氧诱导因子-α（HIF -α）直接控制。在缺氧情况下，HIF -α水平升高，并直接诱导100多个基因的转录，影响从代谢、存活、增殖、迁移到血管生成等多种功能。最近，已经证明有一组特定的微小RNA分子会因缺氧而上调，我们在此将其称为“缺氧相关微小RNA（hypoxamirs）”。特别是，对HIF有响应的缺氧相关微小RNA - 210（miR - 210）是一种独特的微小RNA，它在进化上保守，在缺氧的细胞和组织类型中普遍表达。通过计算机模拟、转录和生化方法已经确定了miR - 210的许多直接靶点，其中一部分已得到广泛验证。因此，miR - 210在机制上与多种已知会影响正常发育生理以及许多缺氧依赖性疾病状态（包括组织缺血、炎症和肿瘤发生）的细胞反应的控制相关联。因此，反映出HIF -α的多效性作用，miR - 210似乎作为一种“主要微小RNA”在缺氧状态下对多种功能的控制发挥作用。
Inadequate oxygen availability or hypoxia induces a complex and still incompletely understood set of adaptations that influence cellular survival and function. Many of these adaptations are directly controlled by a master transcription factor, hypoxia inducible factor-alpha (HIF-α). In response to hypoxia, HIF-α levels increase and directly induce the transcription of >100 genes, influencing functions ranging from metabolism, survival, proliferation, migration, to angiogenesis, among others. Recently, it has been demonstrated that a specific set of microRNA molecules are upregulated by hypoxia, which we denote here as “hypoxamirs.” In particular, the HIF-responsive hypoxamir microRNA-210 (miR-210) is a unique microRNA that is evolutionarily conserved and ubiquitously expressed in hypoxic cell and tissue types. A number of direct targets of miR-210 have been identified by in silico, transcriptional and biochemical methods, a subset of which have been extensively validated. As a result, miR-210 has been mechanistically linked to the control of a wide range of cellular responses known to influence normal developmental physiology as well as a number of hypoxia-dependent disease states, including tissue ischemia, inflammation and tumorigenesis. Thus, reflecting the pleiotropic actions of HIF-α, miR-210 appears to function as a “master microRNA” relevant for the control of diverse functions in the hypoxic state.
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