Department of Pharmacy, Al-Mustaqbal University College, Hilla, Babylon, 51001, Iraq.
National Institute of Laser Enhanced Sciences, University of Cairo, Giza, 12613, Egypt.
Cancer Metastasis Rev. 2024 Mar;43(1):5-27. doi: 10.1007/s10555-023-10129-8. Epub 2023 Aug 8.
The hypoxic environment is prominently witnessed in most solid tumors and is associated with the promotion of cell proliferation, epithelial-mesenchymal transition (EMT), angiogenesis, metabolic reprogramming, therapeutic resistance, and metastasis of tumor cells. All the effects are mediated by the expression of a transcription factor hypoxia-inducible factor-1α (HIF-1α). HIF-1α transcriptionally modulates the expression of genes responsible for all the aforementioned functions. The stability of HIF-1α is regulated by many proteins and non-coding RNAs (ncRNAs). In this article, we have critically discussed the crucial role of ncRNAs [such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), Piwi-interacting RNAs (piRNAs), and transfer RNA (tRNA)-derived small RNAs (tsRNAs)] in the regulation of stability and expression of HIF-1α. We have comprehensively discussed the molecular mechanisms and relationship of HIF-1α with each type of ncRNA in either promotion or repression of human cancers and therapeutic resistance. We have also elaborated on ncRNAs that are in clinical examination for the treatment of cancers. Overall, the majority of aspects concerning the relationship between HIF-1α and ncRNAs have been discussed in this article.
缺氧环境在大多数实体瘤中都很明显，与促进细胞增殖、上皮-间充质转化（EMT）、血管生成、代谢重编程、治疗抵抗和肿瘤细胞转移有关。所有这些作用都是由转录因子缺氧诱导因子-1α（HIF-1α）的表达介导的。HIF-1α 转录调节负责所有上述功能的基因的表达。HIF-1α 的稳定性受许多蛋白质和非编码 RNA（ncRNA）的调节。在本文中，我们批判性地讨论了 ncRNA[如 microRNAs（miRNAs）、长非编码 RNA（lncRNAs）、环状 RNA（circRNAs）、Piwi 相互作用 RNA（piRNAs）和转移 RNA（tRNA）衍生的小 RNA（tsRNAs）]在调节 HIF-1α 的稳定性和表达中的关键作用。我们全面讨论了 HIF-1α 与每种类型的 ncRNA 之间在促进或抑制人类癌症和治疗抵抗中的分子机制和关系。我们还详细阐述了正在临床检查用于癌症治疗的 ncRNA。总的来说，本文讨论了 HIF-1α 与 ncRNA 之间关系的大多数方面。
