Breast cancer-associated SNP rs72755295 is a cis-regulatory variation for human EXO1
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Genetics and Molecular Biology |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572022000500101 |
Resumo: | Abstract Breast cancer is the most common malignant tumor in women. A previous genome-wide association study reports that rs72755295, a SNP locating at intron of EXO1 (exonuclease 1), is associated with breast cancer. Due to the complete linkage disequilibrium between rs72755295 and rs4149909, a nonsynonymous mutation for EXO1, rs4149909 is supposed to be the causal SNP. Since EXO1 is overexpressed in breast carcinoma samples, we hypothesized that the genetic variations in this locus might confer breast cancer risk by regulating EXO1 expression. To substantiate this, a functional genomics study was performed. The dual luciferase assay indicated that G of rs72755295 presents significantly higher relative enhancer activity than A, thus verifying that this SNP can influence gene expression in breast cell. Through chromosome conformation capture it was disclosed that the enhancer containing rs72755295 can interact with the EXO1 promoter. RNA-seq analysis indicated that EXO1 expression is dependent on the rs72755295 genotype. By chromatin immunoprecipitation, the transcription factor PAX6 (paired box 6) was recognized to bind the region spanning rs72755295. In electrophoretic mobility shift assay, G of rs72755295 displays obviously higher binding affinity with nuclear protein than A. Our results indicated that rs72755295 is a cis-regulatory variation for EXO1 and might confer breast cancer risk besides rs4149909. |
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Genetics and Molecular Biology |
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Breast cancer-associated SNP rs72755295 is a cis-regulatory variation for human EXO1Breast cancerEXO1rs72755295rs4149909expression regulationAbstract Breast cancer is the most common malignant tumor in women. A previous genome-wide association study reports that rs72755295, a SNP locating at intron of EXO1 (exonuclease 1), is associated with breast cancer. Due to the complete linkage disequilibrium between rs72755295 and rs4149909, a nonsynonymous mutation for EXO1, rs4149909 is supposed to be the causal SNP. Since EXO1 is overexpressed in breast carcinoma samples, we hypothesized that the genetic variations in this locus might confer breast cancer risk by regulating EXO1 expression. To substantiate this, a functional genomics study was performed. The dual luciferase assay indicated that G of rs72755295 presents significantly higher relative enhancer activity than A, thus verifying that this SNP can influence gene expression in breast cell. Through chromosome conformation capture it was disclosed that the enhancer containing rs72755295 can interact with the EXO1 promoter. RNA-seq analysis indicated that EXO1 expression is dependent on the rs72755295 genotype. By chromatin immunoprecipitation, the transcription factor PAX6 (paired box 6) was recognized to bind the region spanning rs72755295. In electrophoretic mobility shift assay, G of rs72755295 displays obviously higher binding affinity with nuclear protein than A. Our results indicated that rs72755295 is a cis-regulatory variation for EXO1 and might confer breast cancer risk besides rs4149909.Sociedade Brasileira de Genética2022-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572022000500101Genetics and Molecular Biology v.45 n.4 2022reponame:Genetics and Molecular Biologyinstname:Sociedade Brasileira de Genética (SBG)instacron:SBG10.1590/1678-4685-gmb-2021-0420info:eu-repo/semantics/openAccessShi,QiangYao,Xing-YuanWang,Hong-YanLi,Ya-JieZhang,Xin-XinSun,Changeng2022-10-06T00:00:00Zoai:scielo:S1415-47572022000500101Revistahttp://www.gmb.org.br/ONGhttps://old.scielo.br/oai/scielo-oai.php||editor@gmb.org.br1678-46851415-4757opendoar:2022-10-06T00:00Genetics and Molecular Biology - Sociedade Brasileira de Genética (SBG)false |
dc.title.none.fl_str_mv |
Breast cancer-associated SNP rs72755295 is a cis-regulatory variation for human EXO1 |
title |
Breast cancer-associated SNP rs72755295 is a cis-regulatory variation for human EXO1 |
spellingShingle |
Breast cancer-associated SNP rs72755295 is a cis-regulatory variation for human EXO1 Shi,Qiang Breast cancer EXO1 rs72755295 rs4149909 expression regulation |
title_short |
Breast cancer-associated SNP rs72755295 is a cis-regulatory variation for human EXO1 |
title_full |
Breast cancer-associated SNP rs72755295 is a cis-regulatory variation for human EXO1 |
title_fullStr |
Breast cancer-associated SNP rs72755295 is a cis-regulatory variation for human EXO1 |
title_full_unstemmed |
Breast cancer-associated SNP rs72755295 is a cis-regulatory variation for human EXO1 |
title_sort |
Breast cancer-associated SNP rs72755295 is a cis-regulatory variation for human EXO1 |
author |
Shi,Qiang |
author_facet |
Shi,Qiang Yao,Xing-Yuan Wang,Hong-Yan Li,Ya-Jie Zhang,Xin-Xin Sun,Chang |
author_role |
author |
author2 |
Yao,Xing-Yuan Wang,Hong-Yan Li,Ya-Jie Zhang,Xin-Xin Sun,Chang |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Shi,Qiang Yao,Xing-Yuan Wang,Hong-Yan Li,Ya-Jie Zhang,Xin-Xin Sun,Chang |
dc.subject.por.fl_str_mv |
Breast cancer EXO1 rs72755295 rs4149909 expression regulation |
topic |
Breast cancer EXO1 rs72755295 rs4149909 expression regulation |
description |
Abstract Breast cancer is the most common malignant tumor in women. A previous genome-wide association study reports that rs72755295, a SNP locating at intron of EXO1 (exonuclease 1), is associated with breast cancer. Due to the complete linkage disequilibrium between rs72755295 and rs4149909, a nonsynonymous mutation for EXO1, rs4149909 is supposed to be the causal SNP. Since EXO1 is overexpressed in breast carcinoma samples, we hypothesized that the genetic variations in this locus might confer breast cancer risk by regulating EXO1 expression. To substantiate this, a functional genomics study was performed. The dual luciferase assay indicated that G of rs72755295 presents significantly higher relative enhancer activity than A, thus verifying that this SNP can influence gene expression in breast cell. Through chromosome conformation capture it was disclosed that the enhancer containing rs72755295 can interact with the EXO1 promoter. RNA-seq analysis indicated that EXO1 expression is dependent on the rs72755295 genotype. By chromatin immunoprecipitation, the transcription factor PAX6 (paired box 6) was recognized to bind the region spanning rs72755295. In electrophoretic mobility shift assay, G of rs72755295 displays obviously higher binding affinity with nuclear protein than A. Our results indicated that rs72755295 is a cis-regulatory variation for EXO1 and might confer breast cancer risk besides rs4149909. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-01-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572022000500101 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572022000500101 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/1678-4685-gmb-2021-0420 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Sociedade Brasileira de Genética |
publisher.none.fl_str_mv |
Sociedade Brasileira de Genética |
dc.source.none.fl_str_mv |
Genetics and Molecular Biology v.45 n.4 2022 reponame:Genetics and Molecular Biology instname:Sociedade Brasileira de Genética (SBG) instacron:SBG |
instname_str |
Sociedade Brasileira de Genética (SBG) |
instacron_str |
SBG |
institution |
SBG |
reponame_str |
Genetics and Molecular Biology |
collection |
Genetics and Molecular Biology |
repository.name.fl_str_mv |
Genetics and Molecular Biology - Sociedade Brasileira de Genética (SBG) |
repository.mail.fl_str_mv |
||editor@gmb.org.br |
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1752122390705340416 |