Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA.
Curr Pharm Des. 2009;15(33):3861-6. doi: 10.2174/138161209789649367.
Recent studies have established that the regulation of microRNAs (miRs) is a feature of the hypoxic response. In this review, we discuss the role of hypoxia-regulated miRs, with an emphasis on miR-210 and miR-373, and anticipate directions for clinical applications. The induction of miR-210 and miR-373 is dependent upon hypoxia inducible factor (HIF), and their up-regulation has been detected in a variety of solid tumors. Both miRs have been associated with adverse prognosis and metastatic potential. The increased expression of miR-210 is linked to an in vivo hypoxic signature. MiR-210 also participates in endothelial and neuronal cells' response to oxygen deprivation and may possess a role in the regulation of angiogenesis. A variety of miR-210 and miR-373 targets that may be relevant to hypoxia have been validated or proposed. Very recently, targets of these miRs that are implicated in DNA repair have been identified, thus establishing an additional link between the hypoxic tumor microenvironment and DNA damage. Extending beyond cancer biology, some of miR-210 targets are likely involved in the regulation of angiogenesis, and neuronal cell survival. Inactivation of miRs affected by hypoxia presents a promising therapeutic strategy in the case of difficult-to-treat cancers, as well as in other non-cancer-related diseases.
最近的研究已经证实，miRNAs（微小 RNA）的调控是低氧反应的一个特征。在这篇综述中，我们讨论了受低氧调节的 miRs 的作用，重点是 miR-210 和 miR-373，并预测了其临床应用的方向。miR-210 和 miR-373 的诱导依赖于缺氧诱导因子（HIF），并且在各种实体瘤中都检测到了它们的上调。这两种 miR 都与不良预后和转移潜能有关。miR-210 表达的增加与体内低氧特征有关。miR-210 还参与内皮细胞和神经元细胞对缺氧的反应，可能在调节血管生成中发挥作用。已经验证或提出了多种与低氧相关的 miR-210 和 miR-373 靶标。最近，这些 miR 的 DNA 修复靶点已被确定，从而在缺氧肿瘤微环境与 DNA 损伤之间建立了另一个联系。超出癌症生物学的范围，miR-210 的一些靶标可能参与了血管生成和神经元细胞存活的调控。受低氧影响的 miRs 的失活在治疗困难的癌症以及其他非癌症相关疾病方面提出了一个很有前途的治疗策略。
