Regulation of Cancer-Associated miRNAs Expression under Hypoxic Conditions

Figure 1

Regulation of miRNAs expression in hypoxia. (a) Illustrates the structure of the HIF-1α protein domain and regulation by miRNAs. (b) Indicates the down- and upregulation of miRNAs in hypoxia. The regulatory feedback pathways are indicated in parentheses. Prolyl hydroxylases (PHD); O₂-dependent degradation domain (ODD); von Hippel–Lindau protein (pVHL); transactivation domains N and C (TAD-N and TAD-C); HIF-1α-inhibitory factor (FIH-1); nuclear localization sequences (NLS). Upon entering the cell nucleus, HIF-1α and HIF-1β combine to form a heterodimer, which binds to hypoxia response elements (HRE, 5′-TACGTGCT-3′) present in multiple genes related to cancer progression. RAS p21 protein activator 1 (RASA1), TP63, tumor protein P63; SNHG1, small nucleolar RNA host gene 1; and mitochondrial transcription factor A (TFAM); Akt, protein kinase B; tissue inhibitor of metalloproteinases 2 (TIMP2); ATG5, autophagy type 5 protein; fibroblast growth factor receptor 3 (FGFR3).

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