Paraquat-induced oxidative stress regulates N6-methyladenosine (m6A) modification of long noncoding RNAs in Neuro-2a cells

Qianqian Su; Nengzhou Chen; Jianping Tang; Junxiang Wang; Wei-Chun Chou; Fuli Zheng; Wenya Shao; Guangxia Yu; Ping Cai; Zhenkun Guo; Minghua He; Huangyuan Li; Siying Wu

Ecotoxicology and Environmental Safety (Jun 2022)

Paraquat-induced oxidative stress regulates N6-methyladenosine (m6A) modification of long noncoding RNAs in Neuro-2a cells

Qianqian Su,
Nengzhou Chen,
Jianping Tang,
Junxiang Wang,
Wei-Chun Chou,
Fuli Zheng,
Wenya Shao,
Guangxia Yu,
Ping Cai,
Zhenkun Guo,
Minghua He,
Huangyuan Li,
Siying Wu

Affiliations

Qianqian Su: Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China
Nengzhou Chen: Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China
Jianping Tang: Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China
Junxiang Wang: Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China
Wei-Chun Chou: Department of Environmental and Global Health and Center for Environmental and Human Toxicology, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA
Fuli Zheng: Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China; The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, China
Wenya Shao: Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China; The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, China
Guangxia Yu: Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China; The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, China
Ping Cai: Department of Environmental and Global Health and Center for Environmental and Human Toxicology, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA; The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Department of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Fuzhou 350122, China
Zhenkun Guo: The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, China
Minghua He: The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Correspondence to: School of Public Health, Fujian Medical University, Fuzhou 350122, China.
Huangyuan Li: Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China; The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Corresponding author at: Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China.
Siying Wu: Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Corresponding author at: Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350122, China.

Journal volume & issue: Vol. 237
p. 113503

Abstract

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Paraquat (PQ) is a ubiquitously applied herbicide. Long-term PQ exposure with low dose has been reported to induce abnormal expression of long non-coding RNAs (lncRNAs) in brain nerve cells, which could further lead to Parkinson's disease (PD). N6-methyladenosine (m6A) modification has recently been identified as having an important role in regulating the function of lncRNAs. However, how m6A modification regulates lncRNAs following PQ exposure remains largely unknown. Herein, this study reported m6A modification of lncRNAs in mouse neuroblastoma cells (Neuro-2a) following PQ induced reactive oxide species (ROS). M6A sequencing was performed to explore the m6A modificated pattern of lncRNAs in Neuro-2a cells which were treated with 200 μM PQ for 3 h. It was found that PQ hypermethylated total RNA and changed the expression of m6A methyltransferase and demethylase proteins, which leading to the alteration of m6A modification of lncRNAs. Furthermore, the functional analysis further revealed that N-acetyl-L-cysteine (NAC)，a ROS scavengers, partly reversed PQ-induced distinct m6A modificated pattern of lncRNAs. In addition, tow specific m6A modified lncRNAs were identified: cell division cycle 5-like (lncRNA CDC5L) and signal transducer and activator of transcription 3 (lncRNA STAT3), which could influence downstream autophagy related biological function. In summary, this work could potentially contribute to the new insight of lncRNAs m6A modification mechanism in the field of environmental toxicology.

Published in Ecotoxicology and Environmental Safety

ISSN: 0147-6513 (Print); 1090-2414 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Technology: Environmental technology. Sanitary engineering: Environmental pollution; Geography. Anthropology. Recreation: Environmental sciences
Website: https://www.journals.elsevier.com/ecotoxicology-and-environmental-safety

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