Wang Lingling, Tang Yufu, Zhao Mingjing, Mao Shitao, Wu Lijian, Liu Shuo, Liu Dan, Zhao Guangdan, Wang Xiaoge
Department of Respiratory Medicine, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, People's Republic of China.
Department of Hepatobiliary Surgery, The General Hospital of Shenyang Military Area Command, Shenyang 110016, People's Republic of China.
Life Sci. 2018 Jan 15;193:292-299. doi: 10.1016/j.lfs.2017.09.039. Epub 2017 Sep 29.
To investigate the role of translationally controlled tumor protein (TCTP) in lung cancer development.
A549 and HCC827 cells were transfected with shRNA specifically targeting TCTP mRNA. Cell growth was assessed by colony formation assay and cell counting kit-8. Cell cycle and apoptosis were analyzed by flow cytometry. Cell migration and invasion was measured by scratch and transwell assays. In vivo tumorigenicity was evaluated by tumor xenografts in nude mice.
TCTP-silenced cells displayed a reduced ability of colony formation and a lower rate of proliferation in vitro. Knockdown of TCTP arrested cell cycle at G1 phase and led to downregulated expression of cyclins B1, D1 and E. Moreover, silencing of TCTP induced apoptosis and altered the levels of apoptosis-regulatory proteins such as cleaved caspase-3, Bcl-2, Bax and p53. Silencing of TCTP also inhibited migration and invasion of lung cancer cells. In addition, TCTP-silenced A549 cells, when subcutaneously inoculated in nude mice, formed tumors at a significantly slower rate.
Our in vitro and in vivo data indicate that silencing of TCTP inhibits growth, migration and invasion of lung cancer cells. Thus, TCTP may be a potential target for lung cancer therapy.
研究翻译控制肿瘤蛋白（TCTP）在肺癌发生发展中的作用。
用特异性靶向TCTP mRNA的短发夹RNA（shRNA）转染A549和HCC827细胞。通过集落形成试验和细胞计数试剂盒-8评估细胞生长。通过流式细胞术分析细胞周期和凋亡。通过划痕试验和Transwell试验测量细胞迁移和侵袭。通过裸鼠体内肿瘤异种移植评估体内致瘤性。
TCTP沉默的细胞在体外显示出集落形成能力降低和增殖率降低。TCTP的敲低使细胞周期停滞在G1期，并导致细胞周期蛋白B1、D1和E的表达下调。此外，TCTP的沉默诱导凋亡，并改变凋亡调节蛋白如裂解的半胱天冬酶-3、Bcl-2、Bax和p53的水平。TCTP的沉默也抑制肺癌细胞的迁移和侵袭。此外，TCTP沉默的A549细胞皮下接种于裸鼠时，形成肿瘤的速度明显减慢。
我们的体外和体内数据表明，TCTP的沉默抑制肺癌细胞的生长、迁移和侵袭。因此，TCTP可能是肺癌治疗的潜在靶点。
