Characterization of novel antisense HIF-1α transcripts in human cancers.
Summary of "Characterization of novel antisense HIF-1α transcripts in human cancers."
Whole transcriptome analyses have revealed new classes of long ncRNA (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 specimen. We found that the antisense transcripts are activated in response to partially 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 5' and 3' antisense RNAs are nuclear transcripts. Further analyses by RNA-FISH showed that the 5'aHIF-1α accumulates at the perinuclear cellular compartment and co-localizes with the 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 membrane transport that may regulate the cancer-relevant HIF-1α pathway.
Affiliation
Department of Biochemistry "G. Moruzzi"; University of Bologna; Bologna, Italy.
Journal Details
This article was published in the following journal.
Name: Cell cycle (Georgetown, Tex.)
ISSN: 1551-4005
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21897117
- DOI: http://dx.doi.org/
Medical and Biotech [MESH] Definitions
Rna, Antisense
RNA molecules which hybridize to complementary sequences in either RNA or DNA altering the function of the latter. Endogenous antisense RNAs function as regulators of gene expression by a variety of mechanisms. Synthetic antisense RNAs are used to effect the functioning of specific genes for investigative or therapeutic purposes.
Dna, Antisense
DNA that is complementary to the sense strand. (The sense strand has the same sequence as the mRNA transcript. The antisense strand is the template for mRNA synthesis.) Synthetic antisense DNAs are used to hybridize to complementary sequences in target RNAs or DNAs to effect the functioning of specific genes for investigative or therapeutic purposes.
Alternative Splicing
A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different.
Genotype
The genetic constitution of the individual; the characterization of the genes.
Genes, Apc
Tumor suppressor genes located in the 5q21 region on the long arm of human chromosome 5. The mutation of these genes is associated with familial adenomatous polyposis (ADENOMATOUS POLYPOSIS COLI) and GARDNER SYNDROME, as well as some sporadic colorectal cancers.
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