PFOS暴露对肺癌细胞中信号通路的影响

Impacts of PFOS exposure on signaling pathways in lung cancer cells

为探讨全氟辛烷磺酸盐(PFOS)产生肺毒性的分子机制,采用细胞计数试剂盒(CCK-8)方法测定不同浓度PFOS对A549细胞活性的影响,并用二代测序方法测定PFOS暴露对A549细胞中miRNAs表达的影响,预测异常表达miRNAs的靶基因.通过生物信息学分析推断靶基因参与的信号通路及潜在的生物学功能.结果显示,低浓度PFOS(<200μmol/L)促进A549细胞增殖,高浓度PFOS抑制细胞增殖.暴露于300μmol/L PFOS中24h的A549细胞中108个miRNAs表达量显著上调,63个miRNAs表达量显著下调.差异表达miRNAs通过Ras、Rap1、HIF-1、ErbB和VEGF等信号通路参与细胞增殖、代谢和发育等生物学过程.这表明PFOS可通过影响细胞增殖和诱发炎症反应对肺造成威胁.

The effects of different concentrations of perfluorooctane sulfonate(PFOS)on the viability of A549 cells were determined by the CCK-8 method.The effects of PFOS exposure on miRNAs expression in A549 cells were detected by the next-generation sequencing method to investigate the molecular mechanism of pulmonary toxicity caused by PFOS.Target genes with abnormal expression of miRNAs were predicted,and their involved signaling pathways and potential biological functions were inferred through bioinformatics analysis.The results showed that a low concentration of PFOS(<200μmol/L)promoted the proliferation of A549 cells,while a high concentration of PFOS inhibited the proliferation of A549 cells.The expression levels of 108 miRNAs and 63 miRNAs in A549 cells exposed to 300μmol/L PFOS for 24 h were significantly up-regulated and down-regulated.Differentially expressed miRNAs participate in biological processes such as cell proliferation,metabolic process,and developmental process through signaling pathways such as Ras,Rap1,HIF-1,ErbB,VEGF and so on.This study suggested that PFOS can threaten the lung by affecting cell proliferation and inducing inflammation.