Natural antisense transcripts of hypoxia-inducible factor 1alpha are detected in different normal and tumour human...

Hypoxia-inducible factor 1 is a heterodimeric transcription factor, made up of two subunits called HIF-1alpha and aryl receptor nuclear translocator, that regulates the expression of genes associated with adaptation to reduced oxygen pressure. The HIF-1alpha messenger RNA (mRNA) and protein are both up-regulated in common human cancers where this transcription factor is known to be involved in tumour progression. In renal carcinoma, a natural antisense of HIF-1alpha transcript (aHIF) that is complementary to the 3'untranslated region of HIF-1alpha mRNA has been described. Here, we provide a grown work for further characterisation of this natural antisense and we show that: (1) aHIF is widely expressed in normal foetal and adult human tissues as in tumour tissues. Foetal aHIF expression level is higher than adult one and high enough to affect the HIF-1alpha mRNA/aHIF transcripts ratio; (2) aHIF could expose AU rich elements present in the 3' untranslated region of HIF-1alpha mRNA and thus possibly increase the degradation speed of HIF-1alpha mRNA; and (3) aHIF promoter possesses several putative hypoxia response elements which could explain the overexpression of aHIF under hypoxic conditions, creating a negative loop of regulation of HIF-1alpha expression.