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

被引:95
作者
Bertozzi, Davide [1 ]
Iurlaro, Raffaella [1 ]
Sordet, Olivier [2 ]
Marinello, Jessica [1 ]
Zaffaroni, Nadia [3 ]
Capranico, Giovanni [1 ]
机构
[1] Univ Bologna, Dept Biochem G Moruzzi, Bologna, Italy
[2] UMR 1037 INSERM Univ, Inst Claudius Regaud, Toulouse, France
[3] Fdn Ist Nazl Tumori Milano, Milan, Italy
关键词
HIF-1; alpha; non-coding RNA; DNA topoisomerase I; DNA damage; camptothecin; DNA TOPOISOMERASE-I; DOUBLE-STRAND BREAKS; FULL-LENGTH CDNAS; NONCODING RNAS; GENE-EXPRESSION; MESSENGER-RNA; ACTIVATION; HYPOXIA; SUPPRESSION; INHIBITORS;
D O I
10.4161/cc.10.18.17183
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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-1 alpha) and 3' (3'aHIF-1 alpha) ends of the human HIF-1 alpha 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-1 alpha has a 5' cap and a poly(A(+)) tail, while the 3'aHIF-1 alpha 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-1 alpha 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-1 alpha in nuclear membrane transport that may regulate the cancer-relevant HIF-1 alpha pathway.
引用
收藏
页码:3189 / 3197
页数:9
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