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Novel hub genes and regulatory network related to ferroptosis in tetralogy of Fallot
Ferroptosis is a newly discovered type of cell death mainly triggered by uncontrolled lipid peroxidation, and it could potentially have a significant impact on the development and progression of tetralogy of Fallot (TOF). Our project aims to identify and validate potential genes related to ferroptos...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10619671/ https://www.ncbi.nlm.nih.gov/pubmed/37920788 http://dx.doi.org/10.3389/fped.2023.1177993 |
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author | Wang, Yu Yang, Junjie Lu, Jieru Wang, Qingjie Wang, Jian Zhao, Jianyuan Huang, Yuqiang Sun, Kun |
author_facet | Wang, Yu Yang, Junjie Lu, Jieru Wang, Qingjie Wang, Jian Zhao, Jianyuan Huang, Yuqiang Sun, Kun |
author_sort | Wang, Yu |
collection | PubMed |
description | Ferroptosis is a newly discovered type of cell death mainly triggered by uncontrolled lipid peroxidation, and it could potentially have a significant impact on the development and progression of tetralogy of Fallot (TOF). Our project aims to identify and validate potential genes related to ferroptosis in TOF. We obtained sequencing data of TOF from the GEO database and ferroptosis-related genes from the ferroptosis database. We employed bioinformatics methods to analyze the differentially expressed mRNAs (DEmRNAs) and microRNAs between the normal control group and TOF group and identify DEmRNAs related to ferroptosis. Protein–protein interaction analysis was conducted to screen hub genes. Furthermore, a miRNA–mRNA–TF co-regulatory network was constructed to utilize prediction software. The expression of hub genes was further validated through quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). After conducting the differential gene analysis, we observed that in TOF, 41 upregulated mRNAs and three downregulated mRNAs associated with ferroptosis genes were found. Further Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analysis revealed that these genes were primarily involved in molecular functions and biological processes related to chemical stress, oxidative stress, cellular response to starvation, response to nutrient levels, cellular response to external stimulus, and cellular response to extracellular stimulus. Furthermore, we constructed a miRNA–mRNA–TF co-regulatory network. qRT-PCR analysis of the right ventricular tissues from human cases showed an upregulation in the mRNA levels of KEAP1 and SQSTM1. Our bioinformatics analysis successfully identified 44 potential genes that are associated with ferroptosis in TOF. This finding significantly contributes to our understanding of the molecular mechanisms underlying the development of TOF. Moreover, these findings have the potential to open new avenues for the development of innovative therapeutic approaches for the treatment of this condition. |
format | Online Article Text |
id | pubmed-10619671 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-106196712023-11-02 Novel hub genes and regulatory network related to ferroptosis in tetralogy of Fallot Wang, Yu Yang, Junjie Lu, Jieru Wang, Qingjie Wang, Jian Zhao, Jianyuan Huang, Yuqiang Sun, Kun Front Pediatr Pediatrics Ferroptosis is a newly discovered type of cell death mainly triggered by uncontrolled lipid peroxidation, and it could potentially have a significant impact on the development and progression of tetralogy of Fallot (TOF). Our project aims to identify and validate potential genes related to ferroptosis in TOF. We obtained sequencing data of TOF from the GEO database and ferroptosis-related genes from the ferroptosis database. We employed bioinformatics methods to analyze the differentially expressed mRNAs (DEmRNAs) and microRNAs between the normal control group and TOF group and identify DEmRNAs related to ferroptosis. Protein–protein interaction analysis was conducted to screen hub genes. Furthermore, a miRNA–mRNA–TF co-regulatory network was constructed to utilize prediction software. The expression of hub genes was further validated through quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). After conducting the differential gene analysis, we observed that in TOF, 41 upregulated mRNAs and three downregulated mRNAs associated with ferroptosis genes were found. Further Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analysis revealed that these genes were primarily involved in molecular functions and biological processes related to chemical stress, oxidative stress, cellular response to starvation, response to nutrient levels, cellular response to external stimulus, and cellular response to extracellular stimulus. Furthermore, we constructed a miRNA–mRNA–TF co-regulatory network. qRT-PCR analysis of the right ventricular tissues from human cases showed an upregulation in the mRNA levels of KEAP1 and SQSTM1. Our bioinformatics analysis successfully identified 44 potential genes that are associated with ferroptosis in TOF. This finding significantly contributes to our understanding of the molecular mechanisms underlying the development of TOF. Moreover, these findings have the potential to open new avenues for the development of innovative therapeutic approaches for the treatment of this condition. Frontiers Media S.A. 2023-10-18 /pmc/articles/PMC10619671/ /pubmed/37920788 http://dx.doi.org/10.3389/fped.2023.1177993 Text en © 2023 Wang, Yang, Lu, Wang, Wang, Zhao, Huang and Sun. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pediatrics Wang, Yu Yang, Junjie Lu, Jieru Wang, Qingjie Wang, Jian Zhao, Jianyuan Huang, Yuqiang Sun, Kun Novel hub genes and regulatory network related to ferroptosis in tetralogy of Fallot |
title | Novel hub genes and regulatory network related to ferroptosis in tetralogy of Fallot |
title_full | Novel hub genes and regulatory network related to ferroptosis in tetralogy of Fallot |
title_fullStr | Novel hub genes and regulatory network related to ferroptosis in tetralogy of Fallot |
title_full_unstemmed | Novel hub genes and regulatory network related to ferroptosis in tetralogy of Fallot |
title_short | Novel hub genes and regulatory network related to ferroptosis in tetralogy of Fallot |
title_sort | novel hub genes and regulatory network related to ferroptosis in tetralogy of fallot |
topic | Pediatrics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10619671/ https://www.ncbi.nlm.nih.gov/pubmed/37920788 http://dx.doi.org/10.3389/fped.2023.1177993 |
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