Organophosphate flame retardant TDCPP: A risk factor for renal cancer?
Organophosphate flame retardant TDCPP: A risk factor for renal cancer?
复制标题
有机磷阻燃剂 TDCPP：肾癌的危险因素？
DOI：
10.1016/j.chemosphere.2022.135485
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发表时间：
2022-06
期刊：
影响因子：
8.8
通讯作者：
Ninghong Song
中科院分区：
文献类型：
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作者：
Xuan Zhou;Xiang Zhou;Liangyu Yao;Xu Zhang;Rong Cong;Jiaochen Luan;Tongtong Zhang;Ninghong Song
三(1,3-二氯-2-丙基)磷酸酯(TDCPP) 是一种氯化有机磷酸酯阻燃剂(OPFR)，广泛用于各种塑料泡沫、树脂和乳胶中。它可以在人体组织中检测到，包括尿液和牛奶。最近的研究表明，TDCPP 具有神经毒性、生殖毒性和潜在的致癌性。在我们的研究中，我们提出了一种预测与肿瘤化合物相互作用相关的基因的新方法。我们首先使用比较毒理学基因组学数据库 (CTD) 并下载了肾癌 TDCPP 的潜在相互作用基因。肾透明细胞癌（KIRC）患者的基因表达数据和相应的临床信息来自癌症基因组图谱数据库（TCGA）。基因型组织表达（GTEx）数据库中正常人的数据用于补充计算。经过PharmMapper数据库的预测，并通过Gene Ontology和京都基因与基因组百科全书的验证，选择25个基因构建蛋白质-蛋白质相互作用网络分析。通过Kaplan-Meier分析评估这些基因的预后价值，并选择了四个相互作用基因。基因集变异分析和药物靶点结合预测证明hub基因与肾透明细胞癌存在潜在关系。然后，我们使用 ChEA3（Chip-X 富集分析，版本 3）数据库来预测这些相互作用基因的上游。分子对接用于预测这些转录因子与 TDCPP 的结合以及相互作用基因与 TDCPP 的结合。此外，在细胞系和体内实验中证明了TDCPP的促癌作用。通过 qPCR 和 Western blot 验证相互作用基因的表达。结合结合能和qPCR结果，我们选择EPAS1来验证其在肾癌细胞系中的功能。我们的研究提供了一种预测TDCPP与肾癌之间潜在相互作用基因的新方法，这可能揭示治疗和预防疾病的潜在靶点。
Tris (1,3-dichloro-2-propyl) phosphate (TDCPP), a chlorinated organophosphate flame retardants(OPFRs), is widely used in a range of plastic foams, resins, and latexes. It can be detected in human tissues, including urine, and milk. Recent research has suggested that TDCPP has neurotoxic, reproductive, and potentially carcinogenic. In our study, we proposed a novel method for predicting the gene associated with tumor-compound interactions. We firstly used The Comparative Toxicogenomics Database (CTD) and downloaded potentially interactive genes about TDCPP in renal carcinoma. Gene expression data and the corresponding clinical information of the Kidney renal clear cell cancer (KIRC) patients were obtained from The Cancer Genome Atlas database (TCGA). Data from normal people in The Genotype‐Tissue Expression (GTEx) databases was used to supplement the calculations. After being predicted by PharmMapper database, and validated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, 25 genes were selected to construct protein-protein interaction network analysis. The prognostic value of these genes was evaluated with Kaplan-Meier analysis, and four interactive genes were selected. Gene set variation analysis and drug-target binding prediction proved the hub gene has a potential relationship with renal clear cell carcinoma. We then used the ChEA3 (Chip-X Enrichment Analysis, Version 3) database to predict the upstream of these interactive genes. Molecular docking was used to predict the binding of these transcription factors to TDCPP and interactive genes to TDCPP. Moreover, in cell lines and in vivo experiments demonstrated the cancer-promoting effect of TDCPP. The expression of the interactive genes was verified by qPCR and Western blot. Combining binding energy and qPCR results, we choose EPAS1 to verify its function in renal carcinoma cell lines. Our study provides a novel method to predict the potential interactive genes between TDCPP and renal cancer, which may reveal potential targets for the treatment and prevention of diseases.