Identifying the NEAT1/miR-26b-5p/S100A2 axis as a regulator in Parkinson's disease based on the ferroptosis-related genes.

<h4>Objectives</h4>Parkinson's disease (PD) is a complex neurodegenerative disease with unclear pathogenesis. Some recent studies have shown that there is a close relationship between PD and ferroptosis. We aimed to identify the ferroptosis-related genes (FRGs) and construct competi...

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Main Authors: Taole Li, Jifeng Guo
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0316179
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author Taole Li
Jifeng Guo
author_facet Taole Li
Jifeng Guo
author_sort Taole Li
collection DOAJ
description <h4>Objectives</h4>Parkinson's disease (PD) is a complex neurodegenerative disease with unclear pathogenesis. Some recent studies have shown that there is a close relationship between PD and ferroptosis. We aimed to identify the ferroptosis-related genes (FRGs) and construct competing endogenous RNA (ceRNA) networks to further assess the pathogenesis of PD.<h4>Methods</h4>Expression of 97 substantia nigra (SN) samples were obtained and intersected with FRGs. Bioinformatics analysis, including the gene set enrichment analysis (GSEA), consensus cluster analysis, weight gene co-expression network analysis (WGCNA), and machine learning algorithms, were employed to assess the feasible differentially expressed genes (DEGs). Characteristic signature genes were used to create novel diagnostic models and construct competing endogenous RNA (ceRNA) regulatory network for PD, which were further verified by in vitro experiments and single-cell RNA sequencing (scRNA-seq).<h4>Results</h4>A total of 453 DEGs were identified and 11 FRGs were selected. We sorted the entire PD cohort into two subtypes based on the FRGs and obtained 67 hub genes. According to the five machine algorithms, 4 features (S100A2, GNGT1, NEUROD4, FCN2) were screened and used to create a PD diagnostic model. Corresponding miRNAs and lncRNAs were predicted to construct a ceRNA network. The scRNA-seq and experimental results showed that the signature model had a certain diagnostic effect and lncRNA NEAT1 might regulate the progression of ferroptosis in PD via the NEAT1/miR-26b-5p/S100A2 axis.<h4>Conclusion</h4>The diagnostic signatures based on the four FRGs had certain diagnostic and individual effects. NEAT1/miR-26b-5p/S100A2 axis is associated with ferroptosis in the pathogenesis of PD. Our findings provide new solutions for treating PD.
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spelling doaj-art-aa5648b5cdfc464d9c7e4c602d405c9f2025-01-08T05:32:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011912e031617910.1371/journal.pone.0316179Identifying the NEAT1/miR-26b-5p/S100A2 axis as a regulator in Parkinson's disease based on the ferroptosis-related genes.Taole LiJifeng Guo<h4>Objectives</h4>Parkinson's disease (PD) is a complex neurodegenerative disease with unclear pathogenesis. Some recent studies have shown that there is a close relationship between PD and ferroptosis. We aimed to identify the ferroptosis-related genes (FRGs) and construct competing endogenous RNA (ceRNA) networks to further assess the pathogenesis of PD.<h4>Methods</h4>Expression of 97 substantia nigra (SN) samples were obtained and intersected with FRGs. Bioinformatics analysis, including the gene set enrichment analysis (GSEA), consensus cluster analysis, weight gene co-expression network analysis (WGCNA), and machine learning algorithms, were employed to assess the feasible differentially expressed genes (DEGs). Characteristic signature genes were used to create novel diagnostic models and construct competing endogenous RNA (ceRNA) regulatory network for PD, which were further verified by in vitro experiments and single-cell RNA sequencing (scRNA-seq).<h4>Results</h4>A total of 453 DEGs were identified and 11 FRGs were selected. We sorted the entire PD cohort into two subtypes based on the FRGs and obtained 67 hub genes. According to the five machine algorithms, 4 features (S100A2, GNGT1, NEUROD4, FCN2) were screened and used to create a PD diagnostic model. Corresponding miRNAs and lncRNAs were predicted to construct a ceRNA network. The scRNA-seq and experimental results showed that the signature model had a certain diagnostic effect and lncRNA NEAT1 might regulate the progression of ferroptosis in PD via the NEAT1/miR-26b-5p/S100A2 axis.<h4>Conclusion</h4>The diagnostic signatures based on the four FRGs had certain diagnostic and individual effects. NEAT1/miR-26b-5p/S100A2 axis is associated with ferroptosis in the pathogenesis of PD. Our findings provide new solutions for treating PD.https://doi.org/10.1371/journal.pone.0316179
spellingShingle Taole Li
Jifeng Guo
Identifying the NEAT1/miR-26b-5p/S100A2 axis as a regulator in Parkinson's disease based on the ferroptosis-related genes.
PLoS ONE
title Identifying the NEAT1/miR-26b-5p/S100A2 axis as a regulator in Parkinson's disease based on the ferroptosis-related genes.
title_full Identifying the NEAT1/miR-26b-5p/S100A2 axis as a regulator in Parkinson's disease based on the ferroptosis-related genes.
title_fullStr Identifying the NEAT1/miR-26b-5p/S100A2 axis as a regulator in Parkinson's disease based on the ferroptosis-related genes.
title_full_unstemmed Identifying the NEAT1/miR-26b-5p/S100A2 axis as a regulator in Parkinson's disease based on the ferroptosis-related genes.
title_short Identifying the NEAT1/miR-26b-5p/S100A2 axis as a regulator in Parkinson's disease based on the ferroptosis-related genes.
title_sort identifying the neat1 mir 26b 5p s100a2 axis as a regulator in parkinson s disease based on the ferroptosis related genes
url https://doi.org/10.1371/journal.pone.0316179
work_keys_str_mv AT taoleli identifyingtheneat1mir26b5ps100a2axisasaregulatorinparkinsonsdiseasebasedontheferroptosisrelatedgenes
AT jifengguo identifyingtheneat1mir26b5ps100a2axisasaregulatorinparkinsonsdiseasebasedontheferroptosisrelatedgenes