Transcriptome-Wide Analysis of N6-Methyladenosine-Modified Long Noncoding RNAs in Particulate Matter-Induced Lung Injury.

IF 3.9 3区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES Toxics Pub Date : 2025-01-27 DOI:10.3390/toxics13020098

Yingying Zeng, Guiping Zhu, Wenjun Peng, Hui Cai, Chong Lu, Ling Ye, Meiling Jin, Jian Wang

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Abstract

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.

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背景：N6-甲基腺苷（m6A）修饰在调节受环境因素影响的多种细胞过程中发挥着至关重要的作用。然而，m6A修饰的长非编码RNA（lncRNA）在颗粒物（PM）诱导的肺损伤发病机制中的参与在很大程度上仍未得到探索。我们利用m6A修饰的RNA免疫沉淀测序（MeRIP-seq）来鉴定长非编码RNA（lncRNA）上差异表达的m6A峰。同时，我们还进行了 lncRNA 测序（lncRNA-seq），以确定差异表达的 lncRNA。通过这两种测序方法获得的数据的交叉，确定了小鼠肺组织中的候选 m6A修饰lncRNAs：结果：共确认了644个lncRNA上的664个高甲基化m6A峰和358个lncRNA上的367个低甲基化m6A峰。我们利用生物信息学工具分析了这些m6A修饰的lncRNA的潜在功能和通路，揭示了它们参与调控炎症、免疫反应和代谢相关通路的情况。通过联合分析MeRIP-seq和lncRNA-seq数据，确定了三个关键的m6A修饰lncRNA（lncRNA NR_003508、lncRNA uc008scb.1和lncRNA ENSMUST00000159072），并利用MeRIP-PCR和qRT-PCR对它们进行了验证。编码-非编码基因共表达网络分析显示，m6A修饰的lncRNA NR_003508和uc008scb.1参与调控与炎症和免疫反应相关的通路：本研究首次在转录组范围内对与 PM 诱导的肺损伤相关的 lncRNA 进行了全面的 m6A 甲基化分析，并确定了三个关键的候选 m6A 修饰 lncRNA。这些发现揭示了 PM 诱导肺损伤的新型调控机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxics Chemical 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.