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

被引：1

作者：

Zeng, Yingying ^{[1
,2
]}

Zhu, Guiping ^{[1
,2
]}

Peng, Wenjun ^{[1
,2
]}

Cai, Hui ^{[1
]}

Lu, Chong ^{[1
,2
]}

Ye, Ling ^{[2
]}

Jin, Meiling ^{[2
]}

Wang, Jian ^{[1
]}

机构：

[1] Fudan Univ, Zhongshan Hosp, Dept Pulm Med, Shanghai 200030, Peoples R China

[2] Fudan Univ, Zhongshan Hosp, Dept Allergy, Shanghai 200030, Peoples R China

来源：

TOXICS | 2025年 / 13卷 / 02期

基金：

中国国家自然科学基金;

关键词：

long noncoding RNAs; m(6)A methylation; particulate matter; lung injury; INFLAMMATION;

D O I：

10.3390/toxics13020098

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

Background: N6-methyladenosine (m(6)A) modification plays a crucial role in the regulation of diverse cellular processes influenced by environmental factors. Nevertheless, the involvement of m(6)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(6)A peaks on 644 lncRNAs and 367 hypomethylated m(6)A peaks on 358 lncRNAs are confirmed. We use bioinformatic tools to analyze the potential functions and pathways of these m(6)A-modified lncRNAs, revealing their involvement in regulating inflammation, immune response, and metabolism-related pathways. Three key m(6)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(6)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(6)A methylation profiling in lncRNAs associated with PM-induced lung injury and identifies three pivotal candidate m(6)A-modified lncRNAs. These findings shed light on a novel regulatory mechanism underlying PM-induced lung injury.

引用

页数：13

共 34 条

[1] Autophagy is essential for ultrafine particle-induced inflammation and mucus hyperproduction in airway epithelium [J].

Chen, Zhi-Hua ;

Wu, Yin-Fang ;

Wang, Ping-Li ;

Wu, Yan-Ping ;

Li, Zhou-Yang ;

Zhao, Yun ;

Zhou, Jie-Sen ;

Zhu, Chen ;

Cao, Chao ;

Mao, Yuan-Yuan ;

Xu, Feng ;

Wang, Bei-Bei ;

Cormier, Stephania A. ;

Ying, Song-Min ;

Li, Wen ;

Shen, Hua-Hao .

AUTOPHAGY, 2016, 12 (02) :297-311

[2] Indoor particulate matter concentrations and air cleaner intervention association with biomarkers in former smokers with COPD [J].

Fawzy, Ashraf ;

Woo, Han ;

Raju, Sarath ;

Belz, Daniel C. ;

Putcha, Nirupama ;

Williams, Marlene S. ;

Mccormack, Meredith C. ;

Kohler, Kirsten ;

Hansel, Nadia N. .

ENVIRONMENTAL RESEARCH, 2024, 243

[3] PM2.5 induces pulmonary microvascular injury in COPD via METTL16-mediated m6A modification [J].

Guo, Xiaolan ;

Lin, Yuyin ;

Lin, Yingnan ;

Zhong, Yue ;

Yu, Hongjiao ;

Huang, Yibin ;

Yang, Jingwen ;

Cai, Ying ;

Liu, FengDong ;

Li, Yuanyuan ;

Zhang, Qian-Qian ;

Dai, Jianwei .

ENVIRONMENTAL POLLUTION, 2022, 303

[4] Melatonin protects against PM2.5-induced lung injury by inhibiting ferroptosis of lung epithelial cells in a Nrf2-dependent manner [J].

Guohua, Fan ;

Tieyuan, Zhu ;

Xinping, Min ;

Juan, Xiong .

ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY, 2021, 223

[5] GATA3/long noncoding RNA MHC-R regulates the immune activity of dendritic cells in chronic obstructive pulmonary disease induced by air pollution particulate matter [J].

He, Fang ;

Wang, Nian ;

Yu, Xiaoyuan ;

Zheng, Yufan ;

Liu, Qun ;

Chen, Qingzi ;

Pu, Jinding ;

Li, Naijian ;

Zou, Weifeng ;

Li, Bing ;

Ran, Pixin .

JOURNAL OF HAZARDOUS MATERIALS, 2022, 438

[6] m6A RNA methylation: from mechanisms to therapeutic potential [J].

He, P. Cody ;

He, Chuan .

EMBO JOURNAL, 2021, 40 (03)

[7] Methyltransferase-like 3 leads to lung injury by up-regulation of interleukin 24 through N6-methyladenosine-dependent mRNA stability and translation efficiency in mice exposed to fine particulate matter 2.5 [J].

He, Xiang ;

Zhang, Lei ;

Liu, Shengbin ;

Wang, Junyi ;

Liu, Yao ;

Xiong, Anying ;

Jiang, Manling ;

Luo, Li ;

Ying, Xiong ;

Li, Guoping .

ENVIRONMENTAL POLLUTION, 2022, 308

[8] Lung adenocarcinoma promotion by air pollutants [J].

Hill, William ;

Lim, Emilia L. ;

Weeden, Clare E. ;

Lee, Claudia ;

Augustine, Marcellus ;

Chen, Kezhong ;

Kuan, Feng-Che ;

Marongiu, Fabio ;

Evans, Edward J., Jr. ;

Moore, David A. ;

Rodrigues, Felipe S. ;

Pich, Oriol ;

Bakker, Bjorn ;

Cha, Hongui ;

Myers, Renelle ;

van Maldegem, Febe ;

Boumelha, Jesse ;

Veeriah, Selvaraju ;

Rowan, Andrew ;

Naceur-Lombardelli, Cristina ;

Karasaki, Takahiro ;

Sivakumar, Monica ;

De, Swapnanil ;

Caswell, Deborah R. ;

Nagano, Ai ;

Black, James R. M. ;

Martinez-Ruiz, Carlos ;

Ryu, Min Hyung ;

Huff, Ryan D. ;

Li, Shijia ;

Fave, Marie-Julie ;

Magness, Alastair ;

Suarez-Bonnet, Alejandro ;

Priestnall, Simon L. ;

Luechtenborg, Margreet ;

Lavelle, Katrina ;

Pethick, Joanna ;

Hardy, Steven ;

McRonald, Fiona E. ;

Lin, Meng-Hung ;

Troccoli, Clara I. ;

Ghosh, Moumita ;

Miller, York E. ;

Merrick, Daniel T. ;

Keith, Robert L. ;

Al Bakir, Maise ;

Bailey, Chris ;

Hill, Mark S. ;

Saal, Lao H. ;

Chen, Yilun .

NATURE, 2023, 616 (7955) :159-+

[9] Prevalence, risk factors, and management of asthma in China: a national cross-sectional study [J].

Huang, Kewu ;

Yang, Ting ;

Xu, Jianying ;

Yang, Lan ;

Zhao, Jianping ;

Zhang, Xiangyan ;

Bai, Chunxue ;

Kang, Jian ;

Ran, Pixin ;

Shen, Huahao ;

Wen, Fuqiang ;

Chen, Yahong ;

Sun, Tieying ;

Shan, Guangliang ;

Lin, Yingxiang ;

Xu, Guodong ;

Wu, Sinan ;

Wang, Chaolong ;

Wang, Ruiying ;

Shi, Zhihong ;

Xu, Yongjian ;

Ye, Xianwei ;

Song, Yuanlin ;

Wang, Qiuyue ;

Zhou, Yumin ;

Li, Wen ;

Ding, Liren ;

Wan, Chun ;

Yao, Wanzhen ;

Guo, Yanfei ;

Xiao, Fei ;

Lu, Yong ;

Peng, Xiaoxia ;

Zhang, Biao ;

Xiao, Dan ;

Wang, Zuomin ;

Chen, Zhengming ;

Bu, Xiaoning ;

Zhang, Hong ;

Zhang, Xiaolei ;

An, Li ;

Zhang, Shu ;

Zhu, Jianguo ;

Cao, Zhixin ;

Zhan, Qingyuan ;

Yang, Yuanhua ;

Liang, Lirong ;

Tong, Xunliang ;

Dai, Huaping ;

Cao, Bin .

LANCET, 2019, 394 (10196) :407-418

[10] Functional Classification and Experimental Dissection of Long Noncoding RNAs [J].

Kopp, Florian ;

Mendell, Joshua T. .

CELL, 2018, 172 (03) :393-407

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