香烟烟雾对人支气管上皮细胞FOXO3基因的组蛋白乙酰化及转录与表达的影响
Effect of Cigarette Smoke on Histone Acetylation , Transcription and Expression of FOXO3 in BEAS-2B Cell
目的:探讨香烟烟雾致人支气管上皮细胞(BEAS-2B)恶性转化过程中组蛋白乙酰化改变及其对FOXO3基因表达的影响。方法:以BEAS-2B细胞作为研究对象,建立香烟暴露致恶性转化的体外模型;利用流式细胞术检测细胞凋亡,检测caspase3/7活性改变;高通量ChIP-Seq检测恶性转化细胞中组蛋白H3K9乙酰化改变,Realtime-PCR和Western blotting检测FOXO3及其下游基因的mRNA和蛋白表达。结果:随染烟程度增加,染毒细胞caspase3/7活性与凋亡率逐渐降低;基因启动子区组蛋白H3K9乙酰化分别有155个升高和892个降低,其中组蛋白低乙酰化的抗凋亡基因FOXO3表达下降,组蛋白去乙酰化酶抑制剂(TSA)处理后表达回复;FOXO3下游凋亡相关基因表达降低。结论:组蛋白H3K9低乙酰化导致FOXO3基因表达降低,在香烟烟雾致BEAS-2B细胞恶性转化的凋亡逃逸过程起着重要作用。
his study aim to investigate the change of histone acetylation and its effect on the expression of FOXO3 gene in the malignant human bronchial epithelial cells (BEAS-2B) induced by cigarette smoke. BEAS-2B cells were maintained in cigarette smoke for long-term exposure; Cell apoptosis was investigated by flow cytometry, and caspase3/7 activity was analyzed; the changes in histone acetylation of malignant cells was analyzed by high-throughput ChIP-Seq detection , the expression level of mRNA and protein of FOXO3 were detected by Realtime-PCR and Western blotting. Results: The caspase3/7 cell activity and apoptosis rate decreased graEffect of Cigarette Smoke on Histone Acetylation, Transcription and Expression of FOXO3 in BEAS-2B Celldually with the increase of tobacco smoke exposure; 155 and 892 genes were determine as high H3K9ac and low H3K9ac in their promoter respectively. Expression of FOXO3 rose up after TSA-treatment. The expression of genes related to apoptosis reduced. Conclusion: low-H3K9ac leads to the decrease of FOXO3 gene expression, which plays an important role in apoptosis escape process of BEAS-2B cell malignant transformation induced by cigarette smoke.
张佳玉、李建祥、余晓凡、王进
基础医学细胞生物学分子生物学
香烟BEAS-2B组蛋白乙酰化FOXO3细胞凋亡
cigarette smokeBEAS-2Bhistone acetylationFOXO3apoptosis
张佳玉,李建祥,余晓凡,王进.香烟烟雾对人支气管上皮细胞FOXO3基因的组蛋白乙酰化及转录与表达的影响[EB/OL].(2018-03-08)[2025-08-16].http://www.paper.edu.cn/releasepaper/content/201803-42.点此复制
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