A ceRNA approach may unveil unexpected contributors to deletion syndromes, the model of 5q- syndrome.
Oncoscience
; 2(10): 872-9, 2015.
Article
em En
| MEDLINE
| ID: mdl-26682279
In genomic deletions, gene haploinsufficiency might directly configure a specific disease phenotype. Nevertheless, in some cases no functional association can be identified between haploinsufficient genes and the deletion-associated phenotype. Transcripts can act as microRNA sponges. The reduction of transcripts from the hemizygous region may increase the availability of specific microRNAs, which in turn may exert in-trans regulation of target genes outside the deleted region, eventually contributing to the phenotype. Here we prospect a competing endogenous RNA (ceRNA) approach for the identification of candidate genes target of epigenetic regulation in deletion syndromes. As a model, we analyzed the 5q- myelodysplastic syndrome. Genes in haploinsufficiency within the common 5q deleted region in CD34+ blasts were identified in silico. Using the miRWalk 2.0 platform, we predicted microRNAs whose availability, and thus activity, could be enhanced by the deletion, and performed a genomewide analysis of the genes outside the 5q deleted region that could be targeted by the predicted miRNAs. The analysis pointed to two genes with altered expression in 5q- transcriptome, which have never been related with 5q- before. The prospected approach allows investigating the global transcriptional effect of genomic deletions, possibly prompting discovery of unsuspected contributors in the deletion-associated phenotype. Moreover, it may help in functionally characterizing previously reported unexpected interactions.
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MEDLINE
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En
Ano de publicação:
2015
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Article