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METTL3 regulates PM2.5-induced cell injury by targeting OSGIN1 in human airway epithelial cells
Journal of Hazardous Materials ( IF 13.6 ) Pub Date : 2021-03-03 , DOI: 10.1016/j.jhazmat.2021.125573
Qi Yuan , Huanhuan Zhu , Hanting Liu , Meilin Wang , Haiyan Chu , Zhengdong Zhang

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 (PM2.5)-induced adverse effects. Thus, we investigated the role of m6A modification in PM2.5-induced airway epithelial cell injury. We observed a methyltransferase-like 3 (METTL3)-dependent induction of m6A modification after PM2.5 treatment in HBE and A549 cells. METTL3 knockdown attenuated PM2.5-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 PM2.5. In conclusion, METTL3 may mediate PM2.5-induced cell injury by targeting OSGIN1 in human airway epithelial cells. Our work uncovered a critical role of METTL3 in PM2.5-induced airway epithelial cell injury and provided insight into the vital role of m6A modification in PM2.5-induced human hazards.



中文翻译:

METTL3通过靶向人气道上皮细胞中的OSGIN1调节PM 2.5诱导的细胞损伤

N 6-甲基腺苷(m 6 A)与外源环境因素引起的细胞生物学过程改变有关。然而,关于m 6 A在空气中细颗粒物(PM 2.5)引起的不利影响中的作用知之甚少。因此,我们调查了m 6 A修饰在PM 2.5诱导的气道上皮细胞损伤中的作用。我们观察到HBE和A549细胞中PM 2.5处理后,m 6 A修饰的甲基转移酶样3(METTL3)依赖性诱导。METTL3敲低减弱了PM 2.5诱导的细胞凋亡和细胞周期停滞。mRNA测序和RNA N 6-甲基腺苷结合蛋白免疫沉淀(Me-RIP)分析鉴定出m 6 A修饰的氧化应激诱导生长抑制剂1(OSGIN1)为METTL3的靶基因。抑制METTL3通过催化其m 6 A修饰而导致OSGIN1的mRNA半衰期较短。敲低METTL3或OSGIN1减弱了PM 2.5诱导的细胞凋亡,细胞周期停滞和自噬。总之,METTL3可通过靶向人气道上皮细胞中的OSGIN1介导PM 2.5诱导的细胞损伤。我们的工作揭示了METTL3在PM 2.5中的关键作用引起的气道上皮细胞损伤,并提供了对m 6 A修饰在PM 2.5引起的人类危害中的重要作用的深入了解。

更新日期:2021-03-15
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