Xie Dongli, Zhou Yang, Luo Xiaogang
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai, China.
School of Textile Science and Engineering/National Engineering Laboratory for Advanced Yarn and Clean Production, Wuhan Textile University, Wuhan, China.
PeerJ. 2019 Mar 4;7:e6455. doi: 10.7717/peerj.6455. eCollection 2019.
Recent studies indicate amorphous silica nanoparticles (SiNPs), one of the widely applied nanomaterials, have potential toxicity in humans and induces cell malignant transformation. However, its carcinogenic mechanisms remain poorly understood. This study's purpose was to investigate the underlying toxic mechanisms of amorphous SiNPs on human lung epithelial cells model by using microarray data.
Microarray dataset GSE82062 was collected from Gene Expression Omnibus database, including three repeats of Beas-2B exposed to amorphous SiNPs for 40 passages and three repeats of passage-matched control Beas-2B cells. Differentially expressed genes (DEGs) were identified using linear models for microarray data method. Protein-protein interaction (PPI) network was constructed using data from the STRING database followed by module analysis. The miRwalk2 database was used to predict the underlying target genes of differentially miRNAs. Function enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool.
A total of 323 genes were identified as DEGs, including 280 downregulated (containing 12 pre-miRNAs) and 43 upregulated genes (containing 29 pre-miRNAs). Function enrichment indicated these genes were involved in translational initiation (i.e., eukaryotic translation initiation factor 4 gamma 2 (EIF4G2), poly (A) binding protein cytoplasmic 1 (PABPC1)), response to reactive oxygen species (i.e., superoxide dismutase 1 (SOD1)) and oxidative phosphorylation (i.e., ATP5H). PABPC1 (degree = 15), ATP5H (degree = 11) and SOD1 (degree = 8)] were proved to be hub genes after PPI-module analyses. ATP5H/SOD1 and EIF4G2/PABPC1 were overlapped with the target genes of differentially expressed pre-miR-3648/572/661 and pre-miR-4521.
Amorphous SiNPs may induce tumorigenesis via influencing ATP5H/SOD1-related oxidative stress, oxidative phosphorylation and EIF4G2/PABPC1-associated translational initiation which may be regulated by miR-3648/572/661 and miR-4521, respectively.
近期研究表明，无定形二氧化硅纳米颗粒（SiNPs）作为广泛应用的纳米材料之一，对人体具有潜在毒性，并可诱导细胞恶性转化。然而，其致癌机制仍知之甚少。本研究旨在利用微阵列数据探讨无定形SiNPs对人肺上皮细胞模型的潜在毒性机制。
从基因表达综合数据库收集微阵列数据集GSE82062，包括暴露于无定形SiNPs 40代的Beas-2B细胞的三个重复样本以及传代匹配的对照Beas-2B细胞的三个重复样本。使用微阵列数据的线性模型方法鉴定差异表达基因（DEGs）。利用STRING数据库的数据构建蛋白质-蛋白质相互作用（PPI）网络，随后进行模块分析。使用miRwalk2数据库预测差异miRNA的潜在靶基因。使用注释、可视化和综合发现数据库（DAVID）在线工具进行功能富集分析。
共鉴定出323个DEGs，包括280个下调基因（含12个前体miRNA）和43个上调基因（含29个前体miRNA）。功能富集表明这些基因参与翻译起始（即真核翻译起始因子4γ2（EIF4G2）、细胞质聚腺苷酸结合蛋白1（PABPC1））、对活性氧的反应（即超氧化物歧化酶1（SOD1））和氧化磷酸化（即ATP合酶亚基H（ATP5H））。经PPI-模块分析后，PABPC1（度=15）、ATP5H（度=11）和SOD1（度=8）被证明是枢纽基因。ATP5H/SOD1和EIF4G2/PABPC1与差异表达的前体miR-3648/572/661和前体miR-4521的靶基因重叠。
无定形SiNPs可能通过影响ATP5H/SOD1相关的氧化应激、氧化磷酸化以及EIF4G2/PABPC1相关的翻译起始来诱导肿瘤发生，而这可能分别受miR-3648/572/661和miR-4521调控。
