Genomics Laboratory, The National Cancer Institute of México, Tlalpan, Mexico City 14080, Mexico.
Functional Genomics Laboratory, Biomedicine Unit, FES-IZTACALA, UNAM, Tlalnepantla 54090, Mexico.
Cells. 2022 Jun 11;11(12):1895. doi: 10.3390/cells11121895.
Hypoxia in cancer is a thoroughly studied phenomenon, and the logical cause of the reduction in oxygen tension is tumor growth itself. While sustained hypoxia leads to death by necrosis in cells, there is an exquisitely regulated mechanism that rescues hypoxic cells from their fatal fate. The accumulation in the cytoplasm of the transcription factor HIF-1α, which, under normoxic conditions, is marked for degradation by a group of oxygen-sensing proteins known as prolyl hydroxylases (PHDs) in association with the von Hippel-Lindau anti-oncogene (VHL) is critical for the cell, as it regulates different mechanisms through the genes it induces. A group of microRNAs whose expression is regulated by HIF, collectively called hypoxaMIRs, have been recognized. In this review, we deal with the hypoxaMIRs that have been shown to be expressed in colorectal cancer. Subsequently, using data mining, we analyze a panel of hypoxaMIRs expressed in both normal and tumor tissues obtained from TCGA. Finally, we assess the impact of these hypoxaMIRs on cancer hallmarks through their target genes.
肿瘤缺氧是一个经过深入研究的现象,氧张力降低的逻辑原因是肿瘤本身的生长。虽然持续的缺氧会导致细胞坏死死亡,但存在一种精细调节的机制,可以使缺氧细胞免于致命命运。在正常氧条件下,转录因子 HIF-1α 会在细胞质中积累,该因子被一组称为脯氨酰羟化酶(PHDs)的氧感应蛋白标记为降解,与 von Hippel-Lindau 抑癌基因(VHL)相关联,这对细胞至关重要,因为它通过诱导的基因调节不同的机制。已经发现了一组通过 HIF 调节表达的 microRNAs,统称为 hypoxaMIRs。在这篇综述中,我们讨论了在结直肠癌中表达的 hypoxaMIRs。随后,我们使用数据挖掘分析了从 TCGA 获得的正常和肿瘤组织中表达的一组 hypoxaMIRs。最后,我们通过靶基因评估这些 hypoxaMIRs 对癌症特征的影响。