The impact of 3'UTR variants on differential expression of candidate cancer susceptibility genes.

Variants in regulatory regions are predicted to play an important role in disease susceptibility of common diseases. Polymorphisms mapping to microRNA (miRNA) binding sites have been shown to disrupt the ability of miRNAs to target genes resulting in differential mRNA and protein expression. Skin tu...

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Autores principales:	Laura E Skeeles, Jessica L Fleming, Kimberly L Mahler, Amanda Ewart Toland
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6dd6bd9439734e0db44ec85f1ad03e86
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spelling	oai:doaj.org-article:6dd6bd9439734e0db44ec85f1ad03e862021-11-18T07:54:46ZThe impact of 3'UTR variants on differential expression of candidate cancer susceptibility genes.1932-620310.1371/journal.pone.0058609https://doaj.org/article/6dd6bd9439734e0db44ec85f1ad03e862013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23472213/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Variants in regulatory regions are predicted to play an important role in disease susceptibility of common diseases. Polymorphisms mapping to microRNA (miRNA) binding sites have been shown to disrupt the ability of miRNAs to target genes resulting in differential mRNA and protein expression. Skin tumor susceptibility 5 (Skts5) was identified as a locus conferring susceptibility to chemically-induced skin cancer in NIH/Ola by SPRET/Outbred F1 backcrosses. To determine if polymorphisms between the strains which mapped to putative miRNA binding sites in the 3' untranslated region (3'UTR) of genes at Skts5 influenced expression, we conducted a systematic evaluation of 3'UTRs of candidate genes across this locus. Nine genes had polymorphisms in their 3'UTRs which fit the linkage data and eight of these contained polymorphisms suspected to interfere with or introduce miRNA binding. 3'UTRs of six genes, Bcap29, Dgkb, Hbp1, Pik3cg, Twistnb, and Tspan13 differentially affected luciferase expression, but did not appear to be differentially regulated by the evaluated miRNAs predicted to bind to only one of the two isoforms. 3'UTRs from four additional genes chosen from the locus that fit less stringent criteria were evaluated. Ifrd1 and Etv1 showed differences and contained polymorphisms predicted to disrupt or create miRNA binding sites but showed no difference in regulation by the miRNAs tested. In summary, multiple 3'UTRs with putative functional variants between susceptible and resistant strains of mice influenced differential expression independent of predicted miRNA binding.Laura E SkeelesJessica L FlemingKimberly L MahlerAmanda Ewart TolandPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e58609 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Laura E Skeeles Jessica L Fleming Kimberly L Mahler Amanda Ewart Toland The impact of 3'UTR variants on differential expression of candidate cancer susceptibility genes.
description	Variants in regulatory regions are predicted to play an important role in disease susceptibility of common diseases. Polymorphisms mapping to microRNA (miRNA) binding sites have been shown to disrupt the ability of miRNAs to target genes resulting in differential mRNA and protein expression. Skin tumor susceptibility 5 (Skts5) was identified as a locus conferring susceptibility to chemically-induced skin cancer in NIH/Ola by SPRET/Outbred F1 backcrosses. To determine if polymorphisms between the strains which mapped to putative miRNA binding sites in the 3' untranslated region (3'UTR) of genes at Skts5 influenced expression, we conducted a systematic evaluation of 3'UTRs of candidate genes across this locus. Nine genes had polymorphisms in their 3'UTRs which fit the linkage data and eight of these contained polymorphisms suspected to interfere with or introduce miRNA binding. 3'UTRs of six genes, Bcap29, Dgkb, Hbp1, Pik3cg, Twistnb, and Tspan13 differentially affected luciferase expression, but did not appear to be differentially regulated by the evaluated miRNAs predicted to bind to only one of the two isoforms. 3'UTRs from four additional genes chosen from the locus that fit less stringent criteria were evaluated. Ifrd1 and Etv1 showed differences and contained polymorphisms predicted to disrupt or create miRNA binding sites but showed no difference in regulation by the miRNAs tested. In summary, multiple 3'UTRs with putative functional variants between susceptible and resistant strains of mice influenced differential expression independent of predicted miRNA binding.
format	article
author	Laura E Skeeles Jessica L Fleming Kimberly L Mahler Amanda Ewart Toland
author_facet	Laura E Skeeles Jessica L Fleming Kimberly L Mahler Amanda Ewart Toland
author_sort	Laura E Skeeles
title	The impact of 3'UTR variants on differential expression of candidate cancer susceptibility genes.
title_short	The impact of 3'UTR variants on differential expression of candidate cancer susceptibility genes.
title_full	The impact of 3'UTR variants on differential expression of candidate cancer susceptibility genes.
title_fullStr	The impact of 3'UTR variants on differential expression of candidate cancer susceptibility genes.
title_full_unstemmed	The impact of 3'UTR variants on differential expression of candidate cancer susceptibility genes.
title_sort	impact of 3'utr variants on differential expression of candidate cancer susceptibility genes.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/6dd6bd9439734e0db44ec85f1ad03e86
work_keys_str_mv	AT lauraeskeeles theimpactof3utrvariantsondifferentialexpressionofcandidatecancersusceptibilitygenes AT jessicalfleming theimpactof3utrvariantsondifferentialexpressionofcandidatecancersusceptibilitygenes AT kimberlylmahler theimpactof3utrvariantsondifferentialexpressionofcandidatecancersusceptibilitygenes AT amandaewarttoland theimpactof3utrvariantsondifferentialexpressionofcandidatecancersusceptibilitygenes AT lauraeskeeles impactof3utrvariantsondifferentialexpressionofcandidatecancersusceptibilitygenes AT jessicalfleming impactof3utrvariantsondifferentialexpressionofcandidatecancersusceptibilitygenes AT kimberlylmahler impactof3utrvariantsondifferentialexpressionofcandidatecancersusceptibilitygenes AT amandaewarttoland impactof3utrvariantsondifferentialexpressionofcandidatecancersusceptibilitygenes
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The impact of 3'UTR variants on differential expression of candidate cancer susceptibility genes.

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