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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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