Exploration and identification of six novel ferroptosis-related hub genes as potential gene signatures for peripheral nerve injury

Specific biomarkers of ferroptosis after peripheral nerve injury (PNI) are still under debate. In this study, 52 differentially expressed ferroptosis-related genes (DE-FRGs) were retrieved from publicly accessible sequencing data of intact and injured samples of rats with sciatic nerve crush injury....

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Main Authors: Yifei Zhang, Chun Chen, Dawei Li, Penghui Chen, Lei Hang, Jun Yang, Jin Xie
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-04-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2023.1156467/full
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author Yifei Zhang
Yifei Zhang
Yifei Zhang
Chun Chen
Chun Chen
Chun Chen
Dawei Li
Dawei Li
Dawei Li
Penghui Chen
Penghui Chen
Penghui Chen
Lei Hang
Jun Yang
Jun Yang
Jun Yang
Jin Xie
Jin Xie
Jin Xie
author_facet Yifei Zhang
Yifei Zhang
Yifei Zhang
Chun Chen
Chun Chen
Chun Chen
Dawei Li
Dawei Li
Dawei Li
Penghui Chen
Penghui Chen
Penghui Chen
Lei Hang
Jun Yang
Jun Yang
Jun Yang
Jin Xie
Jin Xie
Jin Xie
author_sort Yifei Zhang
collection DOAJ
description Specific biomarkers of ferroptosis after peripheral nerve injury (PNI) are still under debate. In this study, 52 differentially expressed ferroptosis-related genes (DE-FRGs) were retrieved from publicly accessible sequencing data of intact and injured samples of rats with sciatic nerve crush injury. Functional enrichment analyses revealed that adipogenesis, mitochondrial gene sets, and pathways of MAPK, p53, and CD28 family were predominantly engaged in ferroptosis after PNI. Next, Cdkn1a, Cdh1, Hif1a, Hmox1, Nfe2l2, and Tgfb1 were investigated as new ferroptosis-associated hub genes after PNI. Subsequently, clustering correlation heatmap shows six hub genes are linked to mitochondria. The immunofluorescence assay at 0, 1, 4, 7, and 14 days indicated the temporal expression patterns of Tgfb1, Hmox1, and Hif1a after PNI were consistent with ferroptosis validated by PI and ROS staining, while Cdh1, Cdkn1a, and Nfe2l2 were the opposite. In summary, this study identified six hub genes as possible ferroptosis-related biomarkers for PNI, which may offer therapeutic targets for peripheral nerve regeneration and provide a therapeutic window for ferroptosis.
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spelling doaj.art-09467ceb92864110a0d5a5fa2622f9bb2023-04-06T05:02:52ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-04-011410.3389/fgene.2023.11564671156467Exploration and identification of six novel ferroptosis-related hub genes as potential gene signatures for peripheral nerve injuryYifei Zhang0Yifei Zhang1Yifei Zhang2Chun Chen3Chun Chen4Chun Chen5Dawei Li6Dawei Li7Dawei Li8Penghui Chen9Penghui Chen10Penghui Chen11Lei Hang12Jun Yang13Jun Yang14Jun Yang15Jin Xie16Jin Xie17Jin Xie18Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaEar Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaEar Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaEar Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaEar Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, ChinaBusiness School, Tianhua College, Shanghai Normal University, Shanghai, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaEar Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaEar Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, ChinaSpecific biomarkers of ferroptosis after peripheral nerve injury (PNI) are still under debate. In this study, 52 differentially expressed ferroptosis-related genes (DE-FRGs) were retrieved from publicly accessible sequencing data of intact and injured samples of rats with sciatic nerve crush injury. Functional enrichment analyses revealed that adipogenesis, mitochondrial gene sets, and pathways of MAPK, p53, and CD28 family were predominantly engaged in ferroptosis after PNI. Next, Cdkn1a, Cdh1, Hif1a, Hmox1, Nfe2l2, and Tgfb1 were investigated as new ferroptosis-associated hub genes after PNI. Subsequently, clustering correlation heatmap shows six hub genes are linked to mitochondria. The immunofluorescence assay at 0, 1, 4, 7, and 14 days indicated the temporal expression patterns of Tgfb1, Hmox1, and Hif1a after PNI were consistent with ferroptosis validated by PI and ROS staining, while Cdh1, Cdkn1a, and Nfe2l2 were the opposite. In summary, this study identified six hub genes as possible ferroptosis-related biomarkers for PNI, which may offer therapeutic targets for peripheral nerve regeneration and provide a therapeutic window for ferroptosis.https://www.frontiersin.org/articles/10.3389/fgene.2023.1156467/fullperipheral nerve regenerationferroptosisbiomarkerbioinformaticshub geneperipheral nerve injury
spellingShingle Yifei Zhang
Yifei Zhang
Yifei Zhang
Chun Chen
Chun Chen
Chun Chen
Dawei Li
Dawei Li
Dawei Li
Penghui Chen
Penghui Chen
Penghui Chen
Lei Hang
Jun Yang
Jun Yang
Jun Yang
Jin Xie
Jin Xie
Jin Xie
Exploration and identification of six novel ferroptosis-related hub genes as potential gene signatures for peripheral nerve injury
Frontiers in Genetics
peripheral nerve regeneration
ferroptosis
biomarker
bioinformatics
hub gene
peripheral nerve injury
title Exploration and identification of six novel ferroptosis-related hub genes as potential gene signatures for peripheral nerve injury
title_full Exploration and identification of six novel ferroptosis-related hub genes as potential gene signatures for peripheral nerve injury
title_fullStr Exploration and identification of six novel ferroptosis-related hub genes as potential gene signatures for peripheral nerve injury
title_full_unstemmed Exploration and identification of six novel ferroptosis-related hub genes as potential gene signatures for peripheral nerve injury
title_short Exploration and identification of six novel ferroptosis-related hub genes as potential gene signatures for peripheral nerve injury
title_sort exploration and identification of six novel ferroptosis related hub genes as potential gene signatures for peripheral nerve injury
topic peripheral nerve regeneration
ferroptosis
biomarker
bioinformatics
hub gene
peripheral nerve injury
url https://www.frontiersin.org/articles/10.3389/fgene.2023.1156467/full
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