Xiong Yin, Xi Sichuan, Gara Sudheer Kumar, Shan Jigui, Gao James, Zhang Mary, Shukla Vivek, Wang Ruihong, Hoang Chuong D, Chen Haobin, Schrump David S
Thoracic Epigenetics Section, Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
The Biomedical Informatics and Data Science, Frederick National Laboratory for Cancer Research, Frederick, Maryland.
JTO Clin Res Rep. 2021 May 8;2(7):100181. doi: 10.1016/j.jtocrr.2021.100181. eCollection 2021 Jul.
Although communal smoking of hookah by means of water pipes is perceived to be a safe alternative to cigarette smoking, the effects of hookah smoke in respiratory epithelia have not been well characterized. This study evaluated epigenomic and transcriptomic effects of hookah smoke relative to cigarette smoke in human respiratory epithelial cells.
Primary normal human small airway epithelial cells from three donors and cdk4 and hTERT-immortalized small airway epithelial cells and human bronchial epithelial cells were cultured for 5 days in normal media with or without cigarette smoke condensates (CSCs) or water pipe condensates (WPCs). Cell count, immunoblot, RNA sequencing, quantitative real-time reverse-transcriptase polymerase chain reaction, methylation-specific polymerase chain reaction, and quantitative chromatin immunoprecipitation techniques were used to compare effects of hookah and cigarette smoke on cell proliferation, global histone marks, gene expression, and promoter-related chromatin structure.
CSC and WPC decreased global H4K16ac and H4K20me3 histone marks and mediated distinct and overlapping cancer-associated transcriptome signatures and pathway modulations that were cell line dependent and stratified across lung cancer cells in a histology-specific manner. Epiregulin encoding a master regulator of EGFR signaling that is overexpressed in lung cancers was up-regulated, whereas FILIP1L and ABI3BP encoding mediators of senescence that are repressed in lung cancers were down-regulated by CSC and WPC. Induction of epiregulin and repression of FILIP1L and ABI3BP by these condensates coincided with unique epigenetic alterations within the respective promoters.
These findings support translational studies to ascertain if hookah-mediated epigenomic and transcriptomic alterations in cultured respiratory epithelia are detectable and clinically relevant in hookah smokers.
尽管通过水烟袋共同吸食水烟被认为是一种比吸烟更安全的选择，但水烟烟雾对呼吸道上皮细胞的影响尚未得到充分表征。本研究评估了水烟烟雾相对于香烟烟雾对人呼吸道上皮细胞的表观基因组和转录组的影响。
将来自三名供体的原代正常人小气道上皮细胞以及cdk4和hTERT永生化的小气道上皮细胞和人支气管上皮细胞在含有或不含有香烟烟雾冷凝物（CSC）或水烟冷凝物（WPC）的正常培养基中培养5天。使用细胞计数、免疫印迹、RNA测序、定量实时逆转录聚合酶链反应、甲基化特异性聚合酶链反应和定量染色质免疫沉淀技术来比较水烟和香烟烟雾对细胞增殖、整体组蛋白标记、基因表达和启动子相关染色质结构的影响。
CSC和WPC降低了整体H4K16ac和H4K20me3组蛋白标记，并介导了不同且重叠的癌症相关转录组特征和途径调节，这些调节依赖于细胞系，并以组织学特异性方式在肺癌细胞中分层。编码在肺癌中过表达的EGFR信号传导主要调节因子的上皮调节素上调，而编码在肺癌中被抑制的衰老介质的FILIP1L和ABI3BP被CSC和WPC下调。这些冷凝物对上皮调节素的诱导以及对FILIP1L和ABI3BP的抑制与各自启动子内独特的表观遗传改变相一致。
这些发现支持进行转化研究，以确定在培养的呼吸道上皮细胞中水烟介导的表观基因组和转录组改变在水烟吸烟者中是否可检测到以及是否与临床相关。
