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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Main Authors:	Skeeles, Laura E., Fleming, Jessica L., Mahler, Kimberly L., Toland, Amanda Ewart
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589377/

id	pubmed-3589377
recordtype	oai_dc
spelling	pubmed-35893772013-03-07 The Impact of 3′UTR Variants on Differential Expression of Candidate Cancer Susceptibility Genes Skeeles, Laura E. Fleming, Jessica L. Mahler, Kimberly L. Toland, Amanda Ewart Research Article 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. Public Library of Science 2013-03-05 /pmc/articles/PMC3589377/ /pubmed/23472213 http://dx.doi.org/10.1371/journal.pone.0058609 Text en © 2013 Skeeles et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Skeeles, Laura E. Fleming, Jessica L. Mahler, Kimberly L. Toland, Amanda Ewart
spellingShingle	Skeeles, Laura E. Fleming, Jessica L. Mahler, Kimberly L. Toland, Amanda Ewart The Impact of 3′UTR Variants on Differential Expression of Candidate Cancer Susceptibility Genes
author_facet	Skeeles, Laura E. Fleming, Jessica L. Mahler, Kimberly L. Toland, Amanda Ewart
author_sort	Skeeles, Laura E.
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
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.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589377/
_version_	1611959913892806656

The Impact of 3′UTR Variants on Differential Expression of Candidate Cancer Susceptibility Genes

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