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The Reticulon-4 3-bp Deletion/Insertion Polymorphism Is Associated with Structural mRNA Changes and the Risk of Breast Cancer: A Population-Based Case–Control Study with Bioinformatics Analysis
Breast cancer (BC) is a complex disease caused by molecular events that disrupt cellular survival and death. Discovering novel biomarkers is still required to better understand and treat BC. The reticulon-4 (RTN4) gene, encoding Nogo proteins, plays a critical role in apoptosis and cancer developmen...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10381770/ https://www.ncbi.nlm.nih.gov/pubmed/37511924 http://dx.doi.org/10.3390/life13071549 |
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author | Pourzand, Pouria Tabasi, Farhad Fayazbakhsh, Fariba Sarhadi, Shamim Bahari, Gholamreza Mohammadi, Mohsen Jomepour, Sahar Nafeli, Mohammad Mosayebi, Fatemeh Heravi, Mehrdad Taheri, Mohsen Hashemi, Mohammad Ghavami, Saeid |
author_facet | Pourzand, Pouria Tabasi, Farhad Fayazbakhsh, Fariba Sarhadi, Shamim Bahari, Gholamreza Mohammadi, Mohsen Jomepour, Sahar Nafeli, Mohammad Mosayebi, Fatemeh Heravi, Mehrdad Taheri, Mohsen Hashemi, Mohammad Ghavami, Saeid |
author_sort | Pourzand, Pouria |
collection | PubMed |
description | Breast cancer (BC) is a complex disease caused by molecular events that disrupt cellular survival and death. Discovering novel biomarkers is still required to better understand and treat BC. The reticulon-4 (RTN4) gene, encoding Nogo proteins, plays a critical role in apoptosis and cancer development, with genetic variations affecting its function. We investigated the rs34917480 in RTN4 and its association with BC risk in an Iranian population sample. We also predicted the rs34917480 effect on RTN4 mRNA structure and explored the RTN4’s protein–protein interaction network (PPIN) and related pathways. In this case–control study, 437 women (212 BC and 225 healthy) were recruited. The rs34917480 was genotyped using AS-PCR, mRNA secondary structure was predicted with RNAfold, and PPIN was constructed using the STRING database. Our findings revealed that this variant was associated with a decreased risk of BC in heterozygous (p = 0.012), dominant (p = 0.015), over-dominant (p = 0.017), and allelic (p = 0.035) models. Our prediction model showed that this variant could modify RTN4’s mRNA thermodynamics and potentially its translation. RTN4’s PPIN also revealed a strong association with apoptosis regulation and key signaling pathways highly implicated in BC. Consequently, our findings, for the first time, demonstrate that rs34917480 could be a protective factor against BC in our cohort, probably via preceding mechanisms. |
format | Online Article Text |
id | pubmed-10381770 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103817702023-07-29 The Reticulon-4 3-bp Deletion/Insertion Polymorphism Is Associated with Structural mRNA Changes and the Risk of Breast Cancer: A Population-Based Case–Control Study with Bioinformatics Analysis Pourzand, Pouria Tabasi, Farhad Fayazbakhsh, Fariba Sarhadi, Shamim Bahari, Gholamreza Mohammadi, Mohsen Jomepour, Sahar Nafeli, Mohammad Mosayebi, Fatemeh Heravi, Mehrdad Taheri, Mohsen Hashemi, Mohammad Ghavami, Saeid Life (Basel) Article Breast cancer (BC) is a complex disease caused by molecular events that disrupt cellular survival and death. Discovering novel biomarkers is still required to better understand and treat BC. The reticulon-4 (RTN4) gene, encoding Nogo proteins, plays a critical role in apoptosis and cancer development, with genetic variations affecting its function. We investigated the rs34917480 in RTN4 and its association with BC risk in an Iranian population sample. We also predicted the rs34917480 effect on RTN4 mRNA structure and explored the RTN4’s protein–protein interaction network (PPIN) and related pathways. In this case–control study, 437 women (212 BC and 225 healthy) were recruited. The rs34917480 was genotyped using AS-PCR, mRNA secondary structure was predicted with RNAfold, and PPIN was constructed using the STRING database. Our findings revealed that this variant was associated with a decreased risk of BC in heterozygous (p = 0.012), dominant (p = 0.015), over-dominant (p = 0.017), and allelic (p = 0.035) models. Our prediction model showed that this variant could modify RTN4’s mRNA thermodynamics and potentially its translation. RTN4’s PPIN also revealed a strong association with apoptosis regulation and key signaling pathways highly implicated in BC. Consequently, our findings, for the first time, demonstrate that rs34917480 could be a protective factor against BC in our cohort, probably via preceding mechanisms. MDPI 2023-07-12 /pmc/articles/PMC10381770/ /pubmed/37511924 http://dx.doi.org/10.3390/life13071549 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Pourzand, Pouria Tabasi, Farhad Fayazbakhsh, Fariba Sarhadi, Shamim Bahari, Gholamreza Mohammadi, Mohsen Jomepour, Sahar Nafeli, Mohammad Mosayebi, Fatemeh Heravi, Mehrdad Taheri, Mohsen Hashemi, Mohammad Ghavami, Saeid The Reticulon-4 3-bp Deletion/Insertion Polymorphism Is Associated with Structural mRNA Changes and the Risk of Breast Cancer: A Population-Based Case–Control Study with Bioinformatics Analysis |
title | The Reticulon-4 3-bp Deletion/Insertion Polymorphism Is Associated with Structural mRNA Changes and the Risk of Breast Cancer: A Population-Based Case–Control Study with Bioinformatics Analysis |
title_full | The Reticulon-4 3-bp Deletion/Insertion Polymorphism Is Associated with Structural mRNA Changes and the Risk of Breast Cancer: A Population-Based Case–Control Study with Bioinformatics Analysis |
title_fullStr | The Reticulon-4 3-bp Deletion/Insertion Polymorphism Is Associated with Structural mRNA Changes and the Risk of Breast Cancer: A Population-Based Case–Control Study with Bioinformatics Analysis |
title_full_unstemmed | The Reticulon-4 3-bp Deletion/Insertion Polymorphism Is Associated with Structural mRNA Changes and the Risk of Breast Cancer: A Population-Based Case–Control Study with Bioinformatics Analysis |
title_short | The Reticulon-4 3-bp Deletion/Insertion Polymorphism Is Associated with Structural mRNA Changes and the Risk of Breast Cancer: A Population-Based Case–Control Study with Bioinformatics Analysis |
title_sort | reticulon-4 3-bp deletion/insertion polymorphism is associated with structural mrna changes and the risk of breast cancer: a population-based case–control study with bioinformatics analysis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10381770/ https://www.ncbi.nlm.nih.gov/pubmed/37511924 http://dx.doi.org/10.3390/life13071549 |
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