Department of Toxicology, School of Public Health, Peking University Health Science Center, Beijing 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, School of Public Health, Peking University Health Science Center, Beijing 100191, PR China; National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing 10021, PR China.
Department of Toxicology, School of Public Health, Peking University Health Science Center, Beijing 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, School of Public Health, Peking University Health Science Center, Beijing 100191, PR China.
Toxicol Appl Pharmacol. 2020 Sep 15;403:115160. doi: 10.1016/j.taap.2020.115160. Epub 2020 Jul 25.
Lung cancer has been the leading cause of cancer incidence and mortality in China for years. Benzo[a]pyrene (BaP) is a well-known carcinogen for lung cancer. To understand alternation of key proteins and their role in BaP-induced lung cancer, we compared proteome profiles between BaP-transformed 16HBE cell line T-16HBE-C1 (THBEc1) cells and control using label-free quantitative proteomic analysis. Forkhead box protein A1 (FOXA1) was selected and evaluated for its potential role in BaP-induced carcinogenesis in vitro and in vivo. Relationship between FOXA1 expression and survival of lung cancer patients were examined via The Cancer Genome Atlas (TCGA) database. A total of 183 differentially expressed proteins were identified, with 67 proteins including FOXA1 up-regulated and 116 proteins down-regulated in THBEc1 cells. Differentially expressed proteins mainly functioned in basic cellular metabolism, tumor related pathways and regulation of transcription factors. FOXA1 knockout inhibited colony formation and migration of THBEc1 cells in vitro. FOXA1 knockout inhibited tumor growth and metastasis in BALB/c-nude mice after subcutaneous and tail vein injection of FOXA1 knockout THBEc1 cells, respectively. FOXA1 mRNA expression was higher in tumor tissues for patients with lung squamous cell carcinoma, but not associated with survival of lung cancer patients. Our findings revealed oncogenic role of FOXA1 in BaP-induced lung cancer and improved understanding of mechanism in BaP-induced carcinogenesis.
多年来，肺癌一直是中国癌症发病率和死亡率的主要原因。苯并[a]芘（BaP）是一种众所周知的肺癌致癌物。为了了解关键蛋白的变化及其在 BaP 诱导的肺癌中的作用，我们使用无标记定量蛋白质组学分析比较了 BaP 转化的 16HBE 细胞系 T-16HBE-C1（THBEc1）细胞和对照之间的蛋白质组谱。选择叉头框蛋白 A1（FOXA1）并评估其在 BaP 诱导的体外和体内致癌作用中的潜在作用。通过癌症基因组图谱（TCGA）数据库检查 FOXA1 表达与肺癌患者生存的关系。鉴定出 183 个差异表达蛋白，其中 67 个蛋白包括 FOXA1 上调和 116 个蛋白下调在 THBEc1 细胞中。差异表达蛋白主要在基本细胞代谢、肿瘤相关途径和转录因子调节中发挥作用。FOXA1 敲除抑制 THBEc1 细胞体外集落形成和迁移。FOXA1 敲除分别抑制 BALB/c-nude 小鼠皮下和尾静脉注射 FOXA1 敲除 THBEc1 细胞后的肿瘤生长和转移。FOXA1 mRNA 表达在肺鳞状细胞癌患者的肿瘤组织中较高，但与肺癌患者的生存无关。我们的研究结果揭示了 FOXA1 在 BaP 诱导的肺癌中的致癌作用，并提高了对 BaP 诱导致癌作用机制的理解。
