转录组分析揭示了与氡致肺癌相关的转录因子。
Transcriptomic analysis reveals transcription factors implicated in radon-induced lung carcinogenesis.
作者信息
Liu Xing, Peng Yuting, Chen Ruobing, Zhou Yueyue, Zou Xihuan, Xia Mingzhu, Wu Xinyi, Yu Meng
机构信息
School of public health, Yangzhou University, No. 136, Jiangyang Middle Road, Hanjiang District, Yangzhou 225009, China.
Department of Otorhinolaryngology-Head and Neck Surgery, The Affiliated Hospital of Yangzhou University, No. 368, hanjiang Middle Road, Hanjiang District, Yangzhou 225009, China.
出版信息
Toxicol Res (Camb). 2024 Oct 3;13(5):tfae161. doi: 10.1093/toxres/tfae161. eCollection 2024 Oct.
BACKGROUND
Radon, a potent carcinogen, is a significant catalyst for lung cancer development. However, the molecular mechanisms triggering radon-induced lung cancer remain elusive.
METHODS
Utilizing a radon exposure concentration of 20,000 Bq/m3 for 20 min/session, malignant transformation was induced in human bronchial epithelial cells (BEAS-2B).
RESULTS
Radon-exposed cells derived from passage 25 (BEAS-2B-Rn) exhibited enhanced proliferation and increased colony formation. Analysis of differential gene expression (DEG) through transcription factors revealed 663 up-regulated and 894 down-regulated genes in radon-exposed cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed significant alterations in the malignant transformation pathway of cells, including those related to cancer and the PI3K/AKT signaling pathway. A PPI network analysis indicated a significant association of oncogenes, such as CCND1, KIT, and GATA3, with lung cancer among differentially expressed genes. In addition, the stability of the housekeeping gene was determined through RT-qPCR analysis, which also confirmed the results of transcriptome analysis.
CONCLUSIONS
The results suggest that transcription factors may play a pivotal role in conferring a survival advantage to radon-exposed cells. This is achieved by malignant transformation of human bronchial epithelial cells into lung carcinogenesis cell phenotypes.
背景
氡是一种强效致癌物，是肺癌发展的重要催化剂。然而，引发氡致肺癌的分子机制仍不清楚。
方法
利用20000 Bq/m3的氡暴露浓度，每次暴露20分钟，诱导人支气管上皮细胞（BEAS-2B）发生恶性转化。
结果
第25代氡暴露细胞（BEAS-2B-Rn）表现出增殖增强和集落形成增加。通过转录因子分析差异基因表达（DEG）发现，氡暴露细胞中有663个基因上调，894个基因下调。基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析显示，细胞恶性转化途径发生了显著改变，包括与癌症和PI3K/AKT信号通路相关的途径。蛋白质-蛋白质相互作用（PPI）网络分析表明，在差异表达基因中，CCND1、KIT和GATA3等癌基因与肺癌存在显著关联。此外，通过RT-qPCR分析确定了管家基因的稳定性，这也证实了转录组分析的结果。
结论
结果表明，转录因子可能在赋予氡暴露细胞生存优势方面发挥关键作用。这是通过将人支气管上皮细胞恶性转化为肺癌细胞表型来实现的。
Zotero 插件