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Genetic Variants in the 3’UTR of BRCA1 and BRCA2 Genes and Their Putative Effects on the microRNA Mechanism in Hereditary Breast and Ovarian Cancer

Hereditary breast and ovarian cancer (HBOC) syndrome is mainly caused by mutations in the BRCA1 and BRCA2 genes. The 3’UTR region allows for the binding of microRNAs, which are involved in genetic tune regulation. We aimed to identify allelic variants on 3’UTR miRNA-binding sites in the BRCA1 and BR...

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Autores principales: Sánchez-Chaparro, María Marisela, Garza-Veloz, Idalia, Zayas-Villanueva, Omar Alejandro, Martinez-Fierro, Margarita L., Delgado-Enciso, Iván, Gomez-Govea, Mayra Alejandra, Martínez-de-Villarreal, Laura Elia, Reséndez-Pérez, Diana, Rodríguez-Sánchez, Iram Pablo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277914/
https://www.ncbi.nlm.nih.gov/pubmed/32414209
http://dx.doi.org/10.3390/diagnostics10050298
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author Sánchez-Chaparro, María Marisela
Garza-Veloz, Idalia
Zayas-Villanueva, Omar Alejandro
Martinez-Fierro, Margarita L.
Delgado-Enciso, Iván
Gomez-Govea, Mayra Alejandra
Martínez-de-Villarreal, Laura Elia
Reséndez-Pérez, Diana
Rodríguez-Sánchez, Iram Pablo
author_facet Sánchez-Chaparro, María Marisela
Garza-Veloz, Idalia
Zayas-Villanueva, Omar Alejandro
Martinez-Fierro, Margarita L.
Delgado-Enciso, Iván
Gomez-Govea, Mayra Alejandra
Martínez-de-Villarreal, Laura Elia
Reséndez-Pérez, Diana
Rodríguez-Sánchez, Iram Pablo
author_sort Sánchez-Chaparro, María Marisela
collection PubMed
description Hereditary breast and ovarian cancer (HBOC) syndrome is mainly caused by mutations in the BRCA1 and BRCA2 genes. The 3’UTR region allows for the binding of microRNAs, which are involved in genetic tune regulation. We aimed to identify allelic variants on 3’UTR miRNA-binding sites in the BRCA1 and BRCA2 genes in HBOC patients. Blood samples were obtained from 50 patients with HBOC and from 50 controls. The 3’UTR regions of BRCA1 and BRCA2 were amplified by PCR and sequenced to identify genetic variants using bioinformatics tools. We detected nine polymorphisms in 3’UTR, namely: four in BRCA1 (rs3092995 (C/G), rs8176318 (C/T), rs111791349 (G/A), and rs12516 (C/T)) and five in BRCA2 (rs15869 (A/C), rs7334543 (A/G), rs1157836 (A/G), and rs75353978 (TT/del TT)). A new variant in position c.*457 (A/C) on 3’UTR of BRCA2 was also identified. The following three variants increased the risk of HBOC in the study population: rs111791349-A, rs15869-C, and c.*457-C (odds ratio (OR) range 3.7–15.4; p < 0.05). Genetic variants into the 3’UTR of BRCA1 and BRCA2 increased the risk of HBOC between 3.7–15.4 times in the study population. The presence/absence of these polymorphisms may influence the loss/creation of miRNA binding sites, such as hsa-miR-1248 in BRCA1 3′UTR or the hsa-miR-548 family binding site in BRCA2. Our results add new evidence of miRNA participation in the pathogenesis of HBOC.
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spelling pubmed-72779142020-06-12 Genetic Variants in the 3’UTR of BRCA1 and BRCA2 Genes and Their Putative Effects on the microRNA Mechanism in Hereditary Breast and Ovarian Cancer Sánchez-Chaparro, María Marisela Garza-Veloz, Idalia Zayas-Villanueva, Omar Alejandro Martinez-Fierro, Margarita L. Delgado-Enciso, Iván Gomez-Govea, Mayra Alejandra Martínez-de-Villarreal, Laura Elia Reséndez-Pérez, Diana Rodríguez-Sánchez, Iram Pablo Diagnostics (Basel) Article Hereditary breast and ovarian cancer (HBOC) syndrome is mainly caused by mutations in the BRCA1 and BRCA2 genes. The 3’UTR region allows for the binding of microRNAs, which are involved in genetic tune regulation. We aimed to identify allelic variants on 3’UTR miRNA-binding sites in the BRCA1 and BRCA2 genes in HBOC patients. Blood samples were obtained from 50 patients with HBOC and from 50 controls. The 3’UTR regions of BRCA1 and BRCA2 were amplified by PCR and sequenced to identify genetic variants using bioinformatics tools. We detected nine polymorphisms in 3’UTR, namely: four in BRCA1 (rs3092995 (C/G), rs8176318 (C/T), rs111791349 (G/A), and rs12516 (C/T)) and five in BRCA2 (rs15869 (A/C), rs7334543 (A/G), rs1157836 (A/G), and rs75353978 (TT/del TT)). A new variant in position c.*457 (A/C) on 3’UTR of BRCA2 was also identified. The following three variants increased the risk of HBOC in the study population: rs111791349-A, rs15869-C, and c.*457-C (odds ratio (OR) range 3.7–15.4; p < 0.05). Genetic variants into the 3’UTR of BRCA1 and BRCA2 increased the risk of HBOC between 3.7–15.4 times in the study population. The presence/absence of these polymorphisms may influence the loss/creation of miRNA binding sites, such as hsa-miR-1248 in BRCA1 3′UTR or the hsa-miR-548 family binding site in BRCA2. Our results add new evidence of miRNA participation in the pathogenesis of HBOC. MDPI 2020-05-13 /pmc/articles/PMC7277914/ /pubmed/32414209 http://dx.doi.org/10.3390/diagnostics10050298 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sánchez-Chaparro, María Marisela
Garza-Veloz, Idalia
Zayas-Villanueva, Omar Alejandro
Martinez-Fierro, Margarita L.
Delgado-Enciso, Iván
Gomez-Govea, Mayra Alejandra
Martínez-de-Villarreal, Laura Elia
Reséndez-Pérez, Diana
Rodríguez-Sánchez, Iram Pablo
Genetic Variants in the 3’UTR of BRCA1 and BRCA2 Genes and Their Putative Effects on the microRNA Mechanism in Hereditary Breast and Ovarian Cancer
title Genetic Variants in the 3’UTR of BRCA1 and BRCA2 Genes and Their Putative Effects on the microRNA Mechanism in Hereditary Breast and Ovarian Cancer
title_full Genetic Variants in the 3’UTR of BRCA1 and BRCA2 Genes and Their Putative Effects on the microRNA Mechanism in Hereditary Breast and Ovarian Cancer
title_fullStr Genetic Variants in the 3’UTR of BRCA1 and BRCA2 Genes and Their Putative Effects on the microRNA Mechanism in Hereditary Breast and Ovarian Cancer
title_full_unstemmed Genetic Variants in the 3’UTR of BRCA1 and BRCA2 Genes and Their Putative Effects on the microRNA Mechanism in Hereditary Breast and Ovarian Cancer
title_short Genetic Variants in the 3’UTR of BRCA1 and BRCA2 Genes and Their Putative Effects on the microRNA Mechanism in Hereditary Breast and Ovarian Cancer
title_sort genetic variants in the 3’utr of brca1 and brca2 genes and their putative effects on the microrna mechanism in hereditary breast and ovarian cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277914/
https://www.ncbi.nlm.nih.gov/pubmed/32414209
http://dx.doi.org/10.3390/diagnostics10050298
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