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

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

doi:10.1016/j.jhazmat.2021.125573

Cited by 41 publications

(23 citation statements)

References 44 publications

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“…Our results revealed that PM 2.5 decreased the viability of normal HBE cells, consistent with our previous studies. [ 28 ] We then hypothesized that PM 2.5 ‐treated HBE cells might secrete EVs to regulate the biological function of neighboring or distant cells. Our coculture experiments indicated that EVs released by PM 2.5 ‐treated HBE cells may induce cytotoxicity in normal HBE cells.…”

Section: Discussionmentioning

confidence: 99%

Fine Particulate Matter Induces Childhood Asthma Attacks via Extracellular Vesicle‐Packaged Let‐7i‐5p‐Mediated Modulation of the MAPK Signaling Pathway

Zheng

Tian

et al. 2021

Advanced Science

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Fine particulate matter less than 2.5 µm in diameter (PM2.5) is a major risk factor for acute asthma attacks in children. However, the biological mechanism underlying this association remains unclear. In the present study, PM2.5‐treated HBE cells‐secreted extracellular vesicles (PM2.5‐EVs) caused cytotoxicity in “horizontal” HBE cells and increased the contractility of “longitudinal” sensitive human bronchial smooth muscle cells (HBSMCs). RNA sequencing showed that let‐7i‐5p is significantly overexpressed in PM2.5‐EVs and asthmatic plasma; additionally, its level is correlated with PM2.5 exposure in children with asthma. The combination of EV‐packaged let‐7i‐5p and the traditional clinical biomarker IgE exhibits the best diagnostic performance (area under the curve [AUC] = 0.855, 95% CI = 0.786–0.923). Mechanistically, let‐7i‐5p is packaged into PM2.5‐EVs by interacting with ELAVL1 and internalized by both “horizontal” recipient HBE cells and “longitudinal” recipient‐sensitive HBSMCs, with subsequent activation of the MAPK signaling pathway via suppression of its target DUSP1. Furthermore, an injection of EV‐packaged let‐7i‐5p into PM2.5‐treated juvenile mice aggravated asthma symptoms. This comprehensive study deciphered the remodeling of the extracellular environment mediated by the secretion of let‐7i‐5p‐enriched EVs during PM2.5‐induced asthma attacks and identified plasma EV‐packaged let‐7i‐5p as a novel predictor of childhood asthma.

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Section: Discussionmentioning

confidence: 99%

Fine Particulate Matter Induces Childhood Asthma Attacks via Extracellular Vesicle‐Packaged Let‐7i‐5p‐Mediated Modulation of the MAPK Signaling Pathway

Zheng

Tian

et al. 2021

Advanced Science

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“…Dysfunction of airway epithelial cells underlies the pathogenesis of airway hyperresponsiveness and inflammation in asthma. A recent study investigated the role of m6A modification in human airway epithelial cells ( 41 ). The results showed that the expression level of methylase METTL3 mRNA and the m6A modification level of total RNA were significantly increased in the human bronchial epithelial (HBE) and A549 cells induced by fine particulate matter (PM 2.5 ).…”

Section: Discussionmentioning

confidence: 99%

“…The results showed that the expression level of methylase METTL3 mRNA and the m6A modification level of total RNA were significantly increased in the human bronchial epithelial (HBE) and A549 cells induced by fine particulate matter (PM 2.5 ). Subsequent findings suggested that the METTL3 protein could maintain the stability of the oxidative stress-induced growth inhibitor 1 ( OSGIN1 ) mRNA by increasing the m6A methylation level and thus participate in PM 2.5 -induced airway epithelial cell damage ( 41 ). Likewise, another recent study examined the role of the demethylase FTO in the differentiation of HBE cells to ciliated cells ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

N6-Methyladenosine Methylomic Landscape of Lung Tissues in Murine Acute Allergic Asthma

et al. 2021

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Allergic asthma is well known as a common respiratory disorder comprising an allergic inflammatory nature and excessive immune characteristic. N6-methyladenosine (m6A) methylation is an RNA epigenetic modification that post-transcriptionally regulates gene expression and function by affecting the RNA fate. Currently, m6A methylation is gaining attention as a mechanism of immunoregulation. However, whether m6A methylation engages the pathological process of asthma remains uncertain. Here, we present the m6A methylomic landscape in the lung tissues of ovalbumin-induced acute asthma mice using MeRIP-seq and RNA-seq. We identified 353 hypermethylated m6A peaks within 329 messenger RNAs (mRNAs) and 150 hypomethylated m6A peaks within 143 mRNAs in the lung tissues of asthmatic mice. These differentially methylated mRNAs were found to be involved in several immune function-relevant signaling pathways. In addition, we predicted 25 RNA-binding proteins that recognize the differentially methylated peak sites by exploring public databases, and the roles of these proteins are mostly related to mRNA biogenesis and metabolism. To further investigate the expression levels of the differentially methylated genes, we performed combined analysis of the m6A methylome and transcriptome data and identified 127 hypermethylated mRNAs (107 high and 20 low expression) and 43 hypomethylated mRNAs with differential expressions (9 high and 34 low expression). Of these, there are a list of mRNAs involved in immune function and regulation. The present results highlight the essential role of m6A methylation in the pathogenesis of asthma.

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“…m 6 A marks are widely distributed in 6990 mRNAs and 250 noncoding RNAs that regulate maturation, transcription, translation, and metabolism and are involved in the modulation of various pathological and physiological activities. Changes in m 6 A levels have profound effects on numerous cellular processes, including autophagy [14], the DNA damage response [15], oxidative stress [16], and tumorigenesis [17]. m 6 A modifications and oxidative stress play complex and contradictory roles in tumorigenesis and development.…”

Section: Introductionmentioning

confidence: 99%

Cross‐Talk between Oxidative Stress and m⁶A RNA Methylation in Cancer

Yang

Chen

2021

Oxidative Medicine and Cellular Longevity

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Oxidative stress is a state of imbalance between oxidation and antioxidation. Excessive ROS levels are an important factor in tumor development. Damage stimulation and excessive activation of oncogenes cause elevated ROS production in cancer, accompanied by an increase in the antioxidant capacity to retain redox homeostasis in tumor cells at an increased level. Although moderate concentrations of ROS produced in cancer cells contribute to maintaining cell survival and cancer progression, massive ROS accumulation can exert toxicity, leading to cancer cell death. RNA modification is a posttranscriptional control mechanism that regulates gene expression and RNA metabolism, and m6A RNA methylation is the most common type of RNA modification in eukaryotes. m6A modifications can modulate cellular ROS levels through different mechanisms. It is worth noting that ROS signaling also plays a regulatory role in m6A modifications. In this review, we concluded the effects of m6A modification and oxidative stress on tumor biological functions. In particular, we discuss the interplay between oxidative stress and m6A modifications.

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

Cited by 41 publications

References 44 publications

Fine Particulate Matter Induces Childhood Asthma Attacks via Extracellular Vesicle‐Packaged Let‐7i‐5p‐Mediated Modulation of the MAPK Signaling Pathway

Fine Particulate Matter Induces Childhood Asthma Attacks via Extracellular Vesicle‐Packaged Let‐7i‐5p‐Mediated Modulation of the MAPK Signaling Pathway

N6-Methyladenosine Methylomic Landscape of Lung Tissues in Murine Acute Allergic Asthma

Cross‐Talk between Oxidative Stress and m⁶A RNA Methylation in Cancer

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

Cited by 41 publications

References 44 publications

Fine Particulate Matter Induces Childhood Asthma Attacks via Extracellular Vesicle‐Packaged Let‐7i‐5p‐Mediated Modulation of the MAPK Signaling Pathway

Fine Particulate Matter Induces Childhood Asthma Attacks via Extracellular Vesicle‐Packaged Let‐7i‐5p‐Mediated Modulation of the MAPK Signaling Pathway

N6-Methyladenosine Methylomic Landscape of Lung Tissues in Murine Acute Allergic Asthma

Cross‐Talk between Oxidative Stress and m6A RNA Methylation in Cancer

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Cross‐Talk between Oxidative Stress and m⁶A RNA Methylation in Cancer