Yingying Zeng, Guiping Zhu, Wenjun Peng, Hui Cai, Chong Lu, Ling Ye, Meiling Jin, Jian Wang
{"title":"Transcriptome-Wide Analysis of N6-Methyladenosine-Modified Long Noncoding RNAs in Particulate Matter-Induced Lung Injury.","authors":"Yingying Zeng, Guiping Zhu, Wenjun Peng, Hui Cai, Chong Lu, Ling Ye, Meiling Jin, Jian Wang","doi":"10.3390/toxics13020098","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>N6-methyladenosine (m<sup>6</sup>A) modification plays a crucial role in the regulation of diverse cellular processes influenced by environmental factors. Nevertheless, the involvement of m<sup>6</sup>A-modified long noncoding RNAs (lncRNAs) in the pathogenesis of lung injury induced by particulate matter (PM) remains largely unexplored.</p><p><strong>Methods: </strong>Here, we establish a mouse model of PM-induced lung injury. We utilized m6A-modified RNA immunoprecipitation sequencing (MeRIP-seq) to identify differentially expressed m6A peaks on long non-coding RNAs (lncRNAs). Concurrently, we performed lncRNA sequencing (lncRNA-seq) to determine the differentially expressed lncRNAs. The candidate m6A-modified lncRNAs in the lung tissues of mice were identified through the intersection of the data obtained from these two sequencing approaches.</p><p><strong>Results: </strong>A total of 664 hypermethylated m<sup>6</sup>A peaks on 644 lncRNAs and 367 hypomethylated m<sup>6</sup>A peaks on 358 lncRNAs are confirmed. We use bioinformatic tools to analyze the potential functions and pathways of these m<sup>6</sup>A-modified lncRNAs, revealing their involvement in regulating inflammation, immune response, and metabolism-related pathways. Three key m<sup>6</sup>A-modified lncRNAs (lncRNA NR_003508, lncRNA uc008scb.1, and lncRNA ENSMUST00000159072) are identified through a joint analysis of the MeRIP-seq and lncRNA-seq data, and their validation is carried out using MeRIP-PCR and qRT-PCR. Analysis of the coding-non-coding gene co-expression network reveals that m<sup>6</sup>A-modified lncRNAs NR_003508 and uc008scb.1 participate in regulating pathways associated with inflammation and immune response.</p><p><strong>Conclusions: </strong>This study first provides a comprehensive transcriptome-wide analysis of m<sup>6</sup>A methylation profiling in lncRNAs associated with PM-induced lung injury and identifies three pivotal candidate m<sup>6</sup>A-modified lncRNAs. These findings shed light on a novel regulatory mechanism underlying PM-induced lung injury.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"13 2","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxics","FirstCategoryId":"93","ListUrlMain":"https://doi.org/10.3390/toxics13020098","RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}
Transcriptome-Wide Analysis of N6-Methyladenosine-Modified Long Noncoding RNAs in Particulate Matter-Induced Lung Injury.
Background: N6-methyladenosine (m6A) modification plays a crucial role in the regulation of diverse cellular processes influenced by environmental factors. Nevertheless, the involvement of m6A-modified long noncoding RNAs (lncRNAs) in the pathogenesis of lung injury induced by particulate matter (PM) remains largely unexplored.
Methods: Here, we establish a mouse model of PM-induced lung injury. We utilized m6A-modified RNA immunoprecipitation sequencing (MeRIP-seq) to identify differentially expressed m6A peaks on long non-coding RNAs (lncRNAs). Concurrently, we performed lncRNA sequencing (lncRNA-seq) to determine the differentially expressed lncRNAs. The candidate m6A-modified lncRNAs in the lung tissues of mice were identified through the intersection of the data obtained from these two sequencing approaches.
Results: A total of 664 hypermethylated m6A peaks on 644 lncRNAs and 367 hypomethylated m6A peaks on 358 lncRNAs are confirmed. We use bioinformatic tools to analyze the potential functions and pathways of these m6A-modified lncRNAs, revealing their involvement in regulating inflammation, immune response, and metabolism-related pathways. Three key m6A-modified lncRNAs (lncRNA NR_003508, lncRNA uc008scb.1, and lncRNA ENSMUST00000159072) are identified through a joint analysis of the MeRIP-seq and lncRNA-seq data, and their validation is carried out using MeRIP-PCR and qRT-PCR. Analysis of the coding-non-coding gene co-expression network reveals that m6A-modified lncRNAs NR_003508 and uc008scb.1 participate in regulating pathways associated with inflammation and immune response.
Conclusions: This study first provides a comprehensive transcriptome-wide analysis of m6A methylation profiling in lncRNAs associated with PM-induced lung injury and identifies three pivotal candidate m6A-modified lncRNAs. These findings shed light on a novel regulatory mechanism underlying PM-induced lung injury.
ToxicsChemical Engineering-Chemical Health and Safety
CiteScore
4.50
自引率
10.90%
发文量
681
审稿时长
6 weeks
期刊介绍：
Toxics (ISSN 2305-6304) is an international, peer-reviewed, open access journal which provides an advanced forum for studies related to all aspects of toxic chemicals and materials. It publishes reviews, regular research papers, and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in detail. There is, therefore, no restriction on the maximum length of the papers, although authors should write their papers in a clear and concise way. The full experimental details must be provided so that the results can be reproduced. Electronic files or software regarding the full details of calculations and experimental procedure can be deposited as supplementary material, if it is not possible to publish them along with the text.
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