METTL3 通过靶向人呼吸道上皮细胞中的 OSGIN1 来调节 PM 诱导的细胞损伤。
METTL3 regulates PM-induced cell injury by targeting OSGIN1 in human airway epithelial cells.
机构信息
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.
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.
出版信息
J Hazard Mater. 2021 Aug 5;415:125573. doi: 10.1016/j.jhazmat.2021.125573. Epub 2021 Mar 3.
N-methyladenosine (mA) is implicated in alteration of cellular biological processes caused by exogenous environmental factors. However, little is known about the role of mA in airborne fine particulate matter (PM)-induced adverse effects. Thus, we investigated the role of mA modification in PM-induced airway epithelial cell injury. We observed a methyltransferase-like 3 (METTL3)-dependent induction of mA modification after PM treatment in HBE and A549 cells. METTL3 knockdown attenuated PM-induced apoptosis and arrest of cell cycle. mRNA sequencing and RNA N-methyladenosine binding protein immunoprecipitation (Me-RIP) assay identified mA-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 mA modification. Knockdown of METTL3 or OSGIN1 attenuated cell apoptosis, arrest of cell cycle and autophagy induced by PM. In conclusion, METTL3 may mediate PM-induced cell injury by targeting OSGIN1 in human airway epithelial cells. Our work uncovered a critical role of METTL3 in PM-induced airway epithelial cell injury and provided insight into the vital role of mA modification in PM-induced human hazards.
N6-甲基腺苷（m6A）参与了细胞生物学过程的改变，这些改变是由外源性环境因素引起的。然而，关于 m6A 在空气中细颗粒物（PM）引起的不良影响中的作用知之甚少。因此，我们研究了 m6A 修饰在 PM 诱导的气道上皮细胞损伤中的作用。我们观察到在 HBE 和 A549 细胞中，PM 处理后，甲基转移酶样 3（METTL3）依赖性诱导 m6A 修饰。METTL3 敲低减弱了 PM 诱导的细胞凋亡和细胞周期阻滞。mRNA 测序和 RNA m6A 结合蛋白免疫沉淀（Me-RIP）分析鉴定出 m6A 修饰的氧化应激诱导生长抑制剂 1（OSGIN1）是 METTL3 的靶基因。METTL3 的敲低通过催化其 m6A 修饰导致 OSGIN1 的 mRNA 半衰期缩短。METTL3 或 OSGIN1 的敲低减弱了 PM 诱导的细胞凋亡、细胞周期阻滞和自噬。总之，METTL3 可能通过靶向人气道上皮细胞中的 OSGIN1 介导 PM 诱导的细胞损伤。我们的工作揭示了 METTL3 在 PM 诱导的气道上皮细胞损伤中的关键作用，并深入了解了 m6A 修饰在 PM 诱导的人类危害中的重要作用。
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