title: A ceRNA approach may unveil unexpected contributors to deletion syndromes, the model of 5q- syndrome.
abstract: 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.
authors.affiliation: Biomedical Department of Internal and Specialized Medicine, Palermo University School of Medicine, Palermo, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Arancio
authors.affiliation: Tumour Immunology Unit, Human Pathology Section, Department of Health Science, Palermo University School of Medicine, Palermo, Italy.
authors.forename: Swonild Ilenia
authors.initials: SI
authors.lastname: Genovese
authors.affiliation: Tumour Immunology Unit, Human Pathology Section, Department of Health Science, Palermo University School of Medicine, Palermo, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Bongiovanni
authors.affiliation: Tumour Immunology Unit, Human Pathology Section, Department of Health Science, Palermo University School of Medicine, Palermo, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Tripodo
keywords: 5q- syndrome; CeRNA; competing endogenous RNAs; genomic deletions; myelodysplastic syndrome