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Functional consequences of cancer associated variants in six human microRNAs

AutorTorruella-Loran, Ignasi; Gallego, Alicia; Balcells, Ingrid; García-Ramallo, Eva; Espinosa-Parrilla, Yolanda
Fecha de publicaciónjun-2014
CitaciónEuropean Human Genetics Conference (2014)
ResumenMicroRNAs are crucial post-transcriptional gene regulators whose strong sequence conservation leads to predict that nucleotide changes in these molecules may be related to disease. We analyzed human microRNA genetic variation and its possible involvement in cancer through a functional approach. From 284 common SNPs (MAF>0.05) located in 254 out of 1872 microRNAs (miRBase Release20.0), 191 were in the precursor microRNA (2.0 SNP/kb), 58 in the mature microRNA (1.5 SNP/kb) and 35 in the microRNA seed region (1.8 SNP/kb). Five of these SNPs, which were previously associated with cancer, were selected for further studies. Three of them (rs12416605, rs35770269 and rs2910164) were in the seed region of miR-938, miR-449c and miR-146a, respectively; one (rs11614913) in the mature miR-196a-2 and the last one (rs3746444) in the mature miR-499b and seed region of miR-499a. Target gene predictions using TargetScan for these microRNA variants revealed that major alleles had a larger number of predicted target genes than minor ones and very little overlap was observed between both alleles in all cases. Furthermore, morphological differences in HeLa cells were observed between the rs3746444 A and G alleles (miR-499a seed) after transfection experiments. Also different expression levels between the C and T rs11614913 alleles (mature miR-196a-2) were detected by RT-qPCR. We are currently investigating the effect of these variants in the spectrum of genes regulated by the studied microRNAs through transcriptome and functional experiments. Different alleles of common microRNA SNPs associated with cancer could lead to changes in microRNA expression and affect their gene regulatory networks.
DescripciónTrabajo presentado en la European Human Genetics Conference, celebrada en Milán del 31 de mayo al 3 de junio de 2014.
URIhttp://hdl.handle.net/10261/156037
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