State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China; Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China; Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Ecotoxicol Environ Saf. 2021 Oct 15;223:112589. doi: 10.1016/j.ecoenv.2021.112589. Epub 2021 Aug 3.
In recent years, organophosphate ester flame retardants (OPFRs), which have been regarded as alternatives for brominated flame retardants (BFRs), have become widely used in building materials, textiles, and electric equipment. Elucidating the relationship between OPFRs and tumors holds great significance for the treatment and prevention of diseases. In this work, we found a new method for predicting the correlation between the interactive genes of OPFRs and tumors. Transcriptome profiles and OPFR information were obtained from The Cancer Genome Atlas and the Genotype-Tissue Expression, Comparative Toxicogenomics, and PharmMapper databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that interactive genes were mainly enriched in prostate cancer, steroid metabolic process, and steroid hormone regulation. Furthermore, protein-protein interaction network analysis revealed 33 biological hub genes. The operating characteristic curves and survival analysis showed the role of key genes in predicting the prognosis of prostate cancer. Gene target prediction and gene set variation analysis proved that OPFRs and their metabolites exert potential effects on prostate cancer. Colony formation assay showed that the cells with AR, mTOR and DDIT3 knockdown could remarkably mitigate the cell proliferation ability in both PC-3 and LNCap cells. Transwell assay demonstrated that the silencing of AR, mTOR and DDIT3 could significantly inhibit the cell invasion capacity of prostate cells. Triphenyl phosphate (TPP) significantly increase the cell proliferation ability and promote cell invasion capacity. AR, mTOR and DDIT3 in the PC-3 and LNCap cells were significantly upregulated with 10-6 M TPP treated.
近年来，有机磷酯阻燃剂（OPFRs）已被视为溴化阻燃剂（BFRs）的替代品，广泛应用于建筑材料、纺织品和电器设备中。阐明 OPFRs 与肿瘤之间的关系对于疾病的治疗和预防具有重要意义。在这项工作中，我们发现了一种预测 OPFRs 与肿瘤相互作用基因相关性的新方法。从癌症基因组图谱（TCGA）和基因型组织表达、比较毒理学基因组学、药物映射器数据库中获取转录组谱和 OPFR 信息。基因本体论和京都基因与基因组百科全书分析表明，相互作用基因主要富集在前列腺癌、类固醇代谢过程和类固醇激素调节中。此外，蛋白质-蛋白质相互作用网络分析揭示了 33 个生物学枢纽基因。工作特征曲线和生存分析显示了关键基因在预测前列腺癌预后中的作用。基因靶标预测和基因集变异分析证明 OPFRs 及其代谢物对前列腺癌具有潜在作用。集落形成实验表明，敲低 AR、mTOR 和 DDIT3 的细胞可显著减轻 PC-3 和 LNCap 细胞的增殖能力。Transwell 实验表明，沉默 AR、mTOR 和 DDIT3 可显著抑制前列腺细胞的侵袭能力。三苯基磷酸酯（TPP）显著增加细胞增殖能力，并促进细胞侵袭能力。用 10-6 M TPP 处理后，PC-3 和 LNCap 细胞中的 AR、mTOR 和 DDIT3 明显上调。
