Factors interacting with HIF-1alpha mRNA: novel therapeutic targets

The heterodimeric transcription factor HIF-1 (hypoxia-inducible factor-1) induces angiogenesis, a process that is aberrantly elevated in cancer. The HIF-1beta subunit is constitutively expressed, but the levels of the HIF-1alpha subunit are robustly regulated, increasing under hypoxic conditions and decreasing in normoxia. These changes result from rapid alterations in the rates of HIF-1alpha production and degradation. While the regulation of HIF-1alpha degradation is understood in significant detail, much less is known about the regulation of HIF-1alpha biosynthesis. Here, we review recent evidence that HIF-1alpha production is effectively controlled by post-transcriptional mechanisms. We focus on the RNA-binding proteins (RBPs) and the non-coding RNAs that interact with the HIF-1alpha mRNA and influence its half-life and translation rate. HIF-1alpha mRNA-binding factors are emerging as promising pharmacological targets to control HIF-1alpha production selectively and efficiently.