Genetic Variants in the 3’UTR of <i>BRCA1</i> and <i>BRCA2</i> 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 <i>BRCA1</i> and <i>BRCA2</i> 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 m...
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MDPI AG
2020-05-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/10/5/298 |
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| author | María Marisela Sánchez-Chaparro Idalia Garza-Veloz Omar Alejandro Zayas-Villanueva Margarita L. Martinez-Fierro Iván Delgado-Enciso Mayra Alejandra Gomez-Govea Laura Elia Martínez-de-Villarreal Diana Reséndez-Pérez Iram Pablo Rodríguez-Sánchez |
| author_facet | María Marisela Sánchez-Chaparro Idalia Garza-Veloz Omar Alejandro Zayas-Villanueva Margarita L. Martinez-Fierro Iván Delgado-Enciso Mayra Alejandra Gomez-Govea Laura Elia Martínez-de-Villarreal Diana Reséndez-Pérez Iram Pablo Rodríguez-Sánchez |
| author_sort | María Marisela Sánchez-Chaparro |
| collection | DOAJ |
| description | Hereditary breast and ovarian cancer (HBOC) syndrome is mainly caused by mutations in the <i>BRCA1</i> and <i>BRCA2</i> 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 <i>BRCA1</i> and <i>BRCA2</i> genes in HBOC patients. Blood samples were obtained from 50 patients with HBOC and from 50 controls. The 3’UTR regions of <i>BRCA1</i> and <i>BRCA2</i> were amplified by PCR and sequenced to identify genetic variants using bioinformatics tools. We detected nine polymorphisms in 3’UTR, namely: four in <i>BRCA1</i> (rs3092995 (C/G), rs8176318 (C/T), rs111791349 (G/A), and rs12516 (C/T)) and five in <i>BRCA2</i> (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 <i>BRCA2</i> 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; <i>p</i> < 0.05). Genetic variants into the 3’UTR of <i>BRCA1</i> and <i>BRCA2</i> 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 <i>BRCA1</i> 3′UTR or the hsa-miR-548 family binding site in <i>BRCA2</i>. Our results add new evidence of miRNA participation in the pathogenesis of HBOC. |
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| spelling | doaj.art-6b0f63b3f48c40fbbd1fb24d0f78c87a2023-11-20T00:22:24ZengMDPI AGDiagnostics2075-44182020-05-0110529810.3390/diagnostics10050298Genetic Variants in the 3’UTR of <i>BRCA1</i> and <i>BRCA2</i> Genes and Their Putative Effects on the microRNA Mechanism in Hereditary Breast and Ovarian CancerMaría Marisela Sánchez-Chaparro0Idalia Garza-Veloz1Omar Alejandro Zayas-Villanueva2Margarita L. Martinez-Fierro3Iván Delgado-Enciso4Mayra Alejandra Gomez-Govea5Laura Elia Martínez-de-Villarreal6Diana Reséndez-Pérez7Iram Pablo Rodríguez-Sánchez8Laboratory of Immunology and Virology, Collage of Biological Sciences, Universidad Autónoma de Nuevo Leon, San Nicolas de los Garza, Nuevo Leon 66451, MexicoMolecular Medicine Laboratory, Human Medicine and HS Academic Unit, Universidad Autonoma de Zacatecas, Zacatecas, Zacatecas 98160, MexicoUniversity Center Against Cancer (CUCC), Hospital Universitario “Dr. José E. González”, Collage of Medicine, Universidad Autónoma de Nuevo Leon, Monterrey, Nuevo Leon 64460, MexicoMolecular Medicine Laboratory, Human Medicine and HS Academic Unit, Universidad Autonoma de Zacatecas, Zacatecas, Zacatecas 98160, MexicoFaculty of Medicine, Universidad de Colima, Colima, Colima 28040, MexicoLaboratory of Molecular and Structural Physiology, Collage of Biological Sciences, Universidad Autonoma de Nuevo Leon, San Nicolas de los Garza, Nuevo Leon 66451, MexicoDepartment of Genetics, Collage of Medicina, Universidad Autonoma de Nuevo Leon, Monterrey, Nuevo Leon 64460, MexicoLaboratory of Immunology and Virology, Collage of Biological Sciences, Universidad Autónoma de Nuevo Leon, San Nicolas de los Garza, Nuevo Leon 66451, MexicoLaboratory of Molecular and Structural Physiology, Collage of Biological Sciences, Universidad Autonoma de Nuevo Leon, San Nicolas de los Garza, Nuevo Leon 66451, MexicoHereditary breast and ovarian cancer (HBOC) syndrome is mainly caused by mutations in the <i>BRCA1</i> and <i>BRCA2</i> 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 <i>BRCA1</i> and <i>BRCA2</i> genes in HBOC patients. Blood samples were obtained from 50 patients with HBOC and from 50 controls. The 3’UTR regions of <i>BRCA1</i> and <i>BRCA2</i> were amplified by PCR and sequenced to identify genetic variants using bioinformatics tools. We detected nine polymorphisms in 3’UTR, namely: four in <i>BRCA1</i> (rs3092995 (C/G), rs8176318 (C/T), rs111791349 (G/A), and rs12516 (C/T)) and five in <i>BRCA2</i> (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 <i>BRCA2</i> 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; <i>p</i> < 0.05). Genetic variants into the 3’UTR of <i>BRCA1</i> and <i>BRCA2</i> 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 <i>BRCA1</i> 3′UTR or the hsa-miR-548 family binding site in <i>BRCA2</i>. Our results add new evidence of miRNA participation in the pathogenesis of HBOC.https://www.mdpi.com/2075-4418/10/5/298hereditary breast and ovarian cancer<i>BRCA1</i><i>BRCA2</i>miRNApolymorphism3’UTR region |
| spellingShingle | María Marisela Sánchez-Chaparro Idalia Garza-Veloz Omar Alejandro Zayas-Villanueva Margarita L. Martinez-Fierro Iván Delgado-Enciso Mayra Alejandra Gomez-Govea Laura Elia Martínez-de-Villarreal Diana Reséndez-Pérez Iram Pablo Rodríguez-Sánchez Genetic Variants in the 3’UTR of <i>BRCA1</i> and <i>BRCA2</i> Genes and Their Putative Effects on the microRNA Mechanism in Hereditary Breast and Ovarian Cancer Diagnostics hereditary breast and ovarian cancer <i>BRCA1</i> <i>BRCA2</i> miRNA polymorphism 3’UTR region |
| title | Genetic Variants in the 3’UTR of <i>BRCA1</i> and <i>BRCA2</i> Genes and Their Putative Effects on the microRNA Mechanism in Hereditary Breast and Ovarian Cancer |
| title_full | Genetic Variants in the 3’UTR of <i>BRCA1</i> and <i>BRCA2</i> Genes and Their Putative Effects on the microRNA Mechanism in Hereditary Breast and Ovarian Cancer |
| title_fullStr | Genetic Variants in the 3’UTR of <i>BRCA1</i> and <i>BRCA2</i> 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 <i>BRCA1</i> and <i>BRCA2</i> Genes and Their Putative Effects on the microRNA Mechanism in Hereditary Breast and Ovarian Cancer |
| title_short | Genetic Variants in the 3’UTR of <i>BRCA1</i> and <i>BRCA2</i> Genes and Their Putative Effects on the microRNA Mechanism in Hereditary Breast and Ovarian Cancer |
| title_sort | genetic variants in the 3 utr of i brca1 i and i brca2 i genes and their putative effects on the microrna mechanism in hereditary breast and ovarian cancer |
| topic | hereditary breast and ovarian cancer <i>BRCA1</i> <i>BRCA2</i> miRNA polymorphism 3’UTR region |
| url | https://www.mdpi.com/2075-4418/10/5/298 |
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