Transcriptome-Wide Analysis of N6-Methyladenosine-Modified Long Noncoding RNAs in Particulate Matter-Induced Lung Injury
Background: 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...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
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| Series: | Toxics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2305-6304/13/2/98 |
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| Summary: | Background: 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. 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 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. Conclusions: 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. |
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| ISSN: | 2305-6304 |