Department of Oncology, Wuxi People's Hospital Affiliated to Nanjing Medical University, 299 Qingyang Road, Wuxi, 214023, China.
The First Clinical Medicine School, Nanjing Medical University, Nanjing, 211166, China.
J Exp Clin Cancer Res. 2020 Feb 3;39(1):27. doi: 10.1186/s13046-020-1535-y.
Hypoxia is a classic characteristic of the tumor microenvironment with a significant impact on cancer progression and therapeutic response. Hypoxia-inducible factor-1 alpha (HIF-1α), the most important transcriptional regulator in the response to hypoxia, has been demonstrated to significantly modulate hypoxic gene expression and signaling transduction networks. In past few decades, growing numbers of studies have revealed the importance of noncoding RNAs (ncRNAs) in hypoxic tumor regions. These hypoxia-responsive ncRNAs (HRNs) play pivotal roles in regulating hypoxic gene expression at the transcriptional, posttranscriptional, translational and posttranslational levels. In addition, as a significant gene expression regulator, ncRNAs exhibit promising roles in regulating HIF-1α expression at multiple levels. In this review, we briefly elucidate the reciprocal regulation between HIF-1α and ncRNAs, as well as their effect on cancer cell behaviors. We also try to summarize the complex feedback loop existing between these two components. Moreover, we evaluated the biomarker potential of HRNs for the diagnosis and prognosis of cancer, as well as the potential clinical utility of shared regulatory mechanisms between HIF-1α and ncRNAs in cancer treatment, providing novel insights into tumorigenicity, which may lead to innovative clinical applications.
缺氧是肿瘤微环境的一个典型特征,对癌症的进展和治疗反应有重大影响。缺氧诱导因子-1α(HIF-1α)是缺氧反应中最重要的转录调节剂,已被证明能显著调节缺氧基因的表达和信号转导网络。在过去几十年中,越来越多的研究揭示了非编码 RNA(ncRNA)在缺氧肿瘤区域的重要性。这些缺氧反应性 ncRNA(HRN)在转录、转录后、翻译和翻译后水平上调节缺氧基因的表达中发挥着关键作用。此外,作为一个重要的基因表达调节剂,ncRNA 在多个水平上调节 HIF-1α的表达也具有很大的潜力。在这篇综述中,我们简要阐明了 HIF-1α和 ncRNA 之间的相互调节作用,以及它们对癌细胞行为的影响。我们还试图总结这两个成分之间存在的复杂反馈回路。此外,我们评估了 HRN 作为癌症诊断和预后的生物标志物的潜力,以及 HIF-1α和 ncRNA 之间共享调节机制在癌症治疗中的潜在临床应用,为肿瘤发生提供了新的见解,这可能导致创新的临床应用。