标题:Reciprocal activation of alpha 5-nAChR and STAT3 in nicotine-induced human lung cancer cell proliferation
作者:Zhang, Yao; Jia, Yanfei; Li, Ping; Li, Huanjie; Xiao, Dongjie; Wang, Yunshan; Ma, Xiaoli
作者机构:[Zhang, Y] Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250100, China;[ Jia, Y] Central Laboratory, Jinan Cent 更多
通讯作者地址:[Wang, YS; Ma, XL]Shandong Univ, Jinan Cent Hosp, Cent Lab, Jinan 250100, Shandong, Peoples R China.
来源:遗传学报
出版年:2017
卷:44
期:7
页码:355-362
DOI:10.1016/j.jgg.2017.03.003
关键词:α5-nAChR;STAT3;Cell proliferation;Nicotine;Non-small cell lung cancer
摘要:Cigarette smoking is the top environmental risk factor for lung cancer.Nicotine,the adclictive component of cigarettes,induces lung cancer cell proliferation,invasion and migration via the activation of nicotinicacetylcholine receptors (nAChRs).Genome-wide association studies (GWAS) show that CHRNA5 gene encoding α5-nAChR is especially relevant to lung cancer.However,the mechanism of this subunit in lung cancer is not clear.In the present study,we demonstrate that the expression of α5-nAChR is correlated with phosphorylated STAT3 (pSTAT3) expression,smoking history and lower survival of non-small cell lung cancer (NSCLC) samples.Nicotine increased the levels of α5-nAChR mRNA and protein in NSCLC cell lines and activated the JAK2/STAT3 signaling cascade.Nicotine-induced activation of JAK2/STAT3 signaling was inhibited by the silencing of α5-nAChR.Characterization of the CHRNA5 promoter revealed four STAT3-response elements.ChIP assays confirmed that the CHRNA5 promoter contains STAT3 binding sites.By silencing STAT3 expression,nicotine-induced upregulation of αS-nAChR was suppressed.Downregulation of αS-nAChR and/or STAT3 expression inhibited nicotine-induced lung cancer cell proliferation.These results suggest that there is a feedback loop between α5-nAChR and STAT3 that contributes to the nicotine-induced tumor cell proliferation,which indicates that α5-nAChR is an important therapeutic target involved in tobacco-associated lung carcinogenesis.
收录类别:CSCD;SCOPUS;SCIE
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85026670730&doi=10.1016%2fj.jgg.2017.03.003&partnerID=40&md5=a8321bc38889d4ae9d71bb933b43a54e
TOP