Hypoxia and Oxygen-Sensing Signaling in Gene Regulation and Cancer Progression.
Hypoxia and Oxygen-Sensing Signaling in Gene Regulation and Cancer Progression.
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DOI：
10.3390/ijms21218162
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发表时间：
2020-10-31
影响因子：
5.6
通讯作者：
Zhang Q
中科院分区：
文献类型：
--
作者：
Yang G;Shi R;Zhang Q
氧稳态调节是调节生理氧变化的最基本的细胞过程，其不规则性导致包括癌症在内的各种人类疾病。缺氧与癌症的发展密切相关，缺氧/氧传感信号在癌症进展的调节中起着关键作用。缺氧/氧传感信号传导的关键分子包括广泛控制氧响应基因的转录调节因子缺氧诱导因子（HIF）、2-酮戊二酸（2-OG）依赖性双加氧酶的中心成员，如脯氨酰羟化酶（PHD或EglN）和用于HIF变性的E3泛素连接酶组分，称为von Hippel-Lindau（编码蛋白pVHL）。本文综述了经典缺氧信号、HIF转录因子和pVHL的研究进展。此外，2-OG依赖性酶，如DNA/RNA修饰酶，JmjC结构域的酶，脯氨酰羟化酶，在癌症进展的基因调控的作用，具体审查。我们还讨论了靶向缺氧和氧传感通路在癌症中的治疗进展。
Oxygen homeostasis regulation is the most fundamental cellular process for adjusting physiological oxygen variations, and its irregularity leads to various human diseases, including cancer. Hypoxia is closely associated with cancer development, and hypoxia/oxygen-sensing signaling plays critical roles in the modulation of cancer progression. The key molecules of the hypoxia/oxygen-sensing signaling include the transcriptional regulator hypoxia-inducible factor (HIF) which widely controls oxygen responsive genes, the central members of the 2-oxoglutarate (2-OG)-dependent dioxygenases, such as prolyl hydroxylase (PHD or EglN), and an E3 ubiquitin ligase component for HIF degeneration called von Hippel–Lindau (encoding protein pVHL). In this review, we summarize the current knowledge about the canonical hypoxia signaling, HIF transcription factors, and pVHL. In addition, the role of 2-OG-dependent enzymes, such as DNA/RNA-modifying enzymes, JmjC domain-containing enzymes, and prolyl hydroxylases, in gene regulation of cancer progression, is specifically reviewed. We also discuss the therapeutic advancement of targeting hypoxia and oxygen sensing pathways in cancer.
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