Hypoxia-inducible factor (HIF), a central regulator for detecting and adapting to cellular oxygen levels, transcriptionally activates genes modulating oxygen homeostasis and metabolic activation. Beyond this, HIF influences many other processes. Hypoxia, in part through HIF-dependent mechanisms, influences epigenetic factors, including DNA methylation and histone acetylation, which modulate hypoxia-responsive gene expression in cells. Hypoxia profoundly affects expression of many noncoding RNAs classes that have clinicopathological implications in cancer. HIF can regulate noncoding RNAs production, while, conversely, noncoding RNAs can modulate HIF expression. There is recent evidence for crosstalk between circadian rhythms and hypoxia-induced signaling, suggesting involvement of molecular clocks in adaptation to fluxes in nutrient and oxygen sensing. HIF induces increased production of cellular vesicles facilitating intercellular communication at a distance—for example, promoting angiogenesis in hypoxic tumors. Understanding the complex networks underlying cellular and genomic regulation in response to hypoxia via HIF may identify novel and specific therapeutic targets.

中文翻译：

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缺氧诱导因子生物学的研究进展

缺氧诱导因子（HIF）是一种检测和适应细胞氧水平的中央调节剂，通过转录激活调节氧稳态和代谢活化的基因。除此之外，HIF还影响许多其他过程。缺氧部分通过HIF依赖性机制影响表观遗传因素，包括DNA甲基化和组蛋白乙酰化，它们调节细胞中缺氧反应性基因的表达。缺氧深刻影响许多在癌症中具有临床病理意义的非编码RNA类别的表达。HIF可以调节非编码RNA的产生，相反，非编码RNA可以调节HIF的表达。最近有证据表明昼夜节律与缺氧诱导的信号传导之间存在串扰，表明分子钟参与了对养分和氧气传感通量的适应。HIF诱导增加了细胞囊泡的产生，从而促进了远距离的细胞间通讯，例如，促进了低氧肿瘤中的血管生成。了解通过HIF对缺氧作出反应的细胞和基因组调控基础的复杂网络可能会确定新的特异性治疗靶标。