γ-突触核蛋白是口腔癌恶性肿瘤中一种新的尼古丁反应蛋白。
Gamma synuclein is a novel nicotine responsive protein in oral cancer malignancy.
作者信息
Hsu Chia-Chen, Su Yu-Fu, Tsai Kuo-Yang, Kuo Feng-Chih, Chiang Chi-Fu, Chien Chu-Yen, Chen Ying-Chen, Lee Chien-Hsing, Wu Yu-Chiao, Wang Kun, Liu Shyun-Yeu, Shieh Yi-Shing
机构信息
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, 114 Taiwan.
Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, 114 Taiwan.
出版信息
Cancer Cell Int. 2020 Jul 10;20:300. doi: 10.1186/s12935-020-01401-w. eCollection 2020.
BACKGROUND
The mechanisms of neuronal protein γ-synuclein (SNCG) in the malignancy of oral squamous cell carcinoma (OSCC) are not clear. This study tested the hypothesis that SNCG is involved in nicotine-induced malignant behaviors of OSCC. The effect of nicotine on SNCG expression and epithelial-to-mesenchymal transition (EMT) markers were examined.
METHODS
Short hairpin RNA (shRNA) and an antagonist specific for α7-nicotine acetylcholine receptors (α7-nAChRs) were used to examine the role of α7-nAChRs in mediating the effects of nicotine. Knockdown of SNCG in nicotine-treated cells was performed to investigate the role of SNCG in cancer malignancy. The in vivo effect of nicotine was examined using a nude mouse xenotransplantation model.
RESULTS
Nicotine increased SNCG expression in a time- and dose-dependent manner. Nicotine treatment also increased E-cadherin and ZO-1 and decreased fibronectin and vimentin expression. After specific knockdown of α7-nAChRs and inhibition of the PI3/AKT signal, the effect of nicotine on SNCG expression was attenuated. Silencing of SNCG abolished nicotine-induced invasion and migration of OSCC cells. The xenotransplantation model revealed that nicotine augmented tumor growth and SNCG expression.
CONCLUSION
Nicotine upregulated SNCG expression by activating the α7-nAChRs/PI3/AKT signaling that are participated in nicotine-induced oral cancer malignancy.
背景
神经元蛋白γ-突触核蛋白（SNCG）在口腔鳞状细胞癌（OSCC）恶性进展中的作用机制尚不清楚。本研究验证了SNCG参与尼古丁诱导的OSCC恶性行为这一假说。检测了尼古丁对SNCG表达及上皮-间质转化（EMT）标志物的影响。
方法
使用短发夹RNA（shRNA）和α7-尼古丁乙酰胆碱受体（α7-nAChRs）特异性拮抗剂来研究α7-nAChRs在介导尼古丁作用中的角色。在尼古丁处理的细胞中敲低SNCG，以研究SNCG在癌症恶性进展中的作用。利用裸鼠异种移植模型检测尼古丁的体内作用。
结果
尼古丁以时间和剂量依赖性方式增加SNCG表达。尼古丁处理还增加了E-钙黏蛋白和紧密连接蛋白1（ZO-1）的表达，并降低了纤连蛋白和波形蛋白的表达。特异性敲低α7-nAChRs并抑制PI3/AKT信号后，尼古丁对SNCG表达的作用减弱。沉默SNCG消除了尼古丁诱导的OSCC细胞侵袭和迁移。异种移植模型显示尼古丁促进肿瘤生长和SNCG表达。
结论
尼古丁通过激活α7-nAChRs/PI3/AKT信号上调SNCG表达，该信号通路参与尼古丁诱导的口腔癌恶性进展。
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