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N6-methyladenosine methylation mediates non-coding RNAs modification in microplastic-induced cardiac injury

Ecotoxicology and Environmental Safety 2023 20 citations ? Citation count from OpenAlex, updated daily. May differ slightly from the publisher's own count.
Min Zhang, Jun Shi, Jun Zhou, Lei Song, Jingjing Ding, Hui ping Deng, Li Weng, Yiqian Zhu, Zhongqing Xu

Summary

Researchers found that microplastic exposure in mice led to accumulation in organs and triggered cell death, particularly affecting heart tissue. Using advanced sequencing techniques, they discovered that microplastics altered chemical modifications (m6A methylation) on non-coding RNA molecules in heart cells, which may disrupt important gene regulatory networks. The study suggests a potential molecular mechanism through which microplastic exposure could contribute to heart damage, though more research is needed to understand the full implications.

Models
Study Type In vivo

Owing to their potential adverse health effects, global contamination by microplastics (MPs) has attracted increased scientific and societal concerns. However, in vivo studies on MP toxicity, along with its effects and underlying mechanisms, remain limited. We recently found that non-coding RNA (ncRNAs) contribute to MP-mediated vascular toxicity. Moreover, previous studies have identified N6-methyladenosine (m6A) modifications in ncRNAs as influencing factors in cardiovascular disease. However, whether and how m6A modifications in ncRNAs are affected by MP-induced cardiotoxicity remain unknown. Herein, we profiled differentially expressed ncRNAs and their related m6A modification profiles in MP-exposed myocardial tissue using RNA sequencing (RNA-seq) and methylated RNA immunoprecipitation sequencing (MeRIP-seq). First, we observed that MPs accumulated in different organs and upregulated apoptosis in the heart, liver, spleen, and kidney cells. Furthermore, total m6A and METTL3 levels increased in the myocardium after exposure to MPs. RNA-seq results revealed that 392 lncRNAs and 302 circRNAs were differentially expressed in MP-treated mouse myocardium compared to the control group. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that these altered lncRNAs and circRNAs were closely associated with endocytosis, cellular senescence, and cell cycle signaling pathways, which may cause cardiotoxicity. Furthermore, MeRIP-seq data showed different distributions and abundances of m6A modifications in lncRNAs and circRNAs. Additionally, we identified differentially m6A methylated lncRNAs and circRNAs through conjoint analysis of the two high-throughput sequencing datasets and found that both m6A modifications and the expression of circ-Arfgef2 and lncG3bp2 were upregulated after exposure to MPs. This suggests that MP-induced m6A modifications in ncRNAs are involved in cardiotoxicity. Our findings contribute to a better understanding of MP-induced cardiotoxicity and new molecular targets for treating cardiac injury.

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