METTL3 regulates PM2.5-induced cell injury by targeting OSGIN1 in human airway epithelial cells

Qi Yuan; Huanhuan Zhu; Hanting Liu; Meilin Wang; Haiyan Chu; Zhengdong Zhang

doi:10.1016/j.jhazmat.2021.125573

METTL3 regulates PM_2.5-induced cell injury by targeting OSGIN1 in human airway epithelial cells

J Hazard Mater. 2021 Aug 5:415:125573. doi: 10.1016/j.jhazmat.2021.125573. Epub 2021 Mar 3.

Authors

Qi Yuan¹, Huanhuan Zhu², Hanting Liu², Meilin Wang², Haiyan Chu³, Zhengdong Zhang⁴

Affiliations

¹ Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Nanjing Municipal Center for Disease Control and Prevention, Nanjing, China.
² Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
³ Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China. Electronic address: chy_grape@njmu.edu.cn.
⁴ Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China. Electronic address: drzdzhang@njmu.edu.cn.

PMID: 33730643
DOI: 10.1016/j.jhazmat.2021.125573

Abstract

N⁶-methyladenosine (m⁶A) is implicated in alteration of cellular biological processes caused by exogenous environmental factors. However, little is known about the role of m⁶A in airborne fine particulate matter (PM_2.5)-induced adverse effects. Thus, we investigated the role of m⁶A modification in PM_2.5-induced airway epithelial cell injury. We observed a methyltransferase-like 3 (METTL3)-dependent induction of m⁶A modification after PM_2.5 treatment in HBE and A549 cells. METTL3 knockdown attenuated PM_2.5-induced apoptosis and arrest of cell cycle. mRNA sequencing and RNA N⁶-methyladenosine binding protein immunoprecipitation (Me-RIP) assay identified m⁶A-modified oxidative stress induced growth inhibitor 1 (OSGIN1) as the target gene of METTL3. Knockdown of METTL3 resulted a shorter mRNA half-life of OSGIN1 by catalyzing its m⁶A modification. Knockdown of METTL3 or OSGIN1 attenuated cell apoptosis, arrest of cell cycle and autophagy induced by PM_2.5. In conclusion, METTL3 may mediate PM_2.5-induced cell injury by targeting OSGIN1 in human airway epithelial cells. Our work uncovered a critical role of METTL3 in PM_2.5-induced airway epithelial cell injury and provided insight into the vital role of m⁶A modification in PM_2.5-induced human hazards.

Keywords: Cell injury; METTL3; N(6)-methyladenosine; OSGIN1; PM(2.5).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autophagy
Epithelial Cells*
Humans
Methyltransferases*
Particulate Matter / toxicity
RNA, Messenger

Substances

Particulate Matter
RNA, Messenger
Methyltransferases
METTL3 protein, human