Characterization of novel antisense HIF-1α transcripts in human cancers

Abstract

Whole transcriptome analyses have revealed new classes of long non coding RNAs (lncRNA), the functions of which are however largely unknown. Recently, we showed that the antitumor DNA topoisomerase I (Top1) inhibitor camptothecin (CPT ) increases the cellular levels of two antisense lncRNAs at the 5′ (5′aHIF-1α) and 3′ (3′aHIF-1α) ends of the human HIF-1α gene. To gain insights into their functions, we have here determined structural and functional aspects of the two antisense RNAs in human cancer cell lines and kidney tumor specimens. We found that the antisense transcripts are activated in response to different kinds of stress, and that the 5′aHIF-1α has a 5′cap and a poly(A+) tail, while the 3′aHIF-1α is known to lack both modifications. Cell fractionation experiments showed that the 5′ and 3′ antisense RNAs are nuclear transcripts. Further analyses by RNA-FISH showed that 5′aHIF-1α accumulates at the perinuclear cellular compartment and co-localizes with nuclear pore complex Nup62 protein, suggesting a role in nuclear membrane trafficking. Finally, we provide evidence that the studied antisense lncRNAs are expressed in human kidney cancer tissues, highlighting their possible roles in cancer development. Altogether, our findings may suggest a novel function of 5′aHIF-1α in nuclear membrane transport that may regulate the cancer-relevant HIF-1α pathway. © 2011 Landes Bioscience.