Methylparaben is most frequently used as an antimicrobial preservative in pharmaceuticals and foods. Methylparaben has been subjected to toxicological studies owing to the increasing concern regarding its possible impact on the environment and human health. However, the cytotoxicity and underlying mechanisms of methylparaben exposure in human lung cells have not been explored. Here, we investigated the effect of methylparaben on cell cycle, apoptotic pathways, and changes in the transcriptome profiles in human lung cells. Our results demonstrate that treatment with methylparaben causes inhibition of cell growth. In addition, methylparaben induced S- and G2/M-phase arrest as a result of enhanced apoptosis. Transcriptome analysis using RNA-seq revealed that mRNA expression of ER stress- and protein misfolding-related gene sets was upregulated in methylparaben-treated group. RNA splicing- and maturation-related gene sets were significantly down-regulated by methylparaben treatment. Interestingly, RNA-seq analysis at the transcript level revealed that alternative splicing events, especially retained intron, were markedly changed by a low dose of methylparaben treatment. Altogether, these data show that methylparaben induces an early phase of apoptosis through cell cycle arrest and downregulation of mRNA maturation.

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可变剪接事件的转录组动力学揭示了对羟基苯甲酸甲酯诱导的H1299人肺癌细胞凋亡的早期阶段。

对羟基苯甲酸甲酯最常用作药物和食品中的抗菌防腐剂。对羟基苯甲酸甲酯由于对其可能对环境和人类健康的影响而日益受到关注，因此已经进行了毒理学研究。但是，尚未探索对羟基苯甲酸甲酯在人肺细胞中的细胞毒性和潜在机制。在这里，我们调查了对羟基苯甲酸甲酯对人肺细胞中细胞周期，凋亡途径和转录组谱变化的影响。我们的结果表明，使用对羟基苯甲酸甲酯治疗会导致细胞生长受到抑制。另外，由于增强的凋亡，对羟基苯甲酸甲酯诱导S期和G2 / M期停滞。使用RNA-seq的转录组分析显示，在对羟基苯甲酸甲酯治疗组中，ER应激和蛋白质错折叠相关基因集的mRNA表达上调。RNA剪接和成熟相关的基因组被对羟基苯甲酸甲酯处理显着下调。有趣的是，转录本水平的RNA-seq分析表明，低剂量的对羟基苯甲酸甲酯处理可显着改变其他剪接事件，尤其是保留的内含子。总而言之，这些数据表明对羟基苯甲酸甲酯通过细胞周期停滞和下调mRNA成熟来诱导凋亡的早期阶段。低剂量的对羟基苯甲酸甲酯处理可显着改变尤其是保留的内含子。总而言之，这些数据表明对羟基苯甲酸甲酯通过细胞周期停滞和下调mRNA成熟来诱导凋亡的早期阶段。低剂量的对羟基苯甲酸甲酯处理可显着改变尤其是保留的内含子。总而言之，这些数据表明对羟基苯甲酸甲酯通过细胞周期停滞和下调mRNA成熟来诱导凋亡的早期阶段。