Downregulation of miR‐218 by nicotine promotes cell proliferation through targeting CDK6 in non–small cell lung cancer

• Published in: Journal of cellular biochemistry 2019-10, Vol.120 (10), p.18370-18377
• Main Authors: Liu, Zhen, Lu, Cuiling, Zhao, Guanren, Han, Xue, Dong, Kaisheng, Wang, Chuanhai, Guan, Jing‐Zhi, Wang, Zhongyuan
• Format: Article
• Language: English
• Subjects: Aged; Blotting, Western; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; CDK6; cell proliferation; Cell Proliferation - drug effects; Cell Proliferation - genetics; Cyclin-Dependent Kinase 6 - genetics; Cyclin-Dependent Kinase 6 - metabolism; Female; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - genetics; Humans; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Male; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miR‐218; nicotine; Nicotine - pharmacology; non–small cell lung cancer
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.29148

Background Nicotine, an important component of tobacco, is a major risk factor of lung cancer, but the mechanism through which nicotine promotes lung cancer development remains unclear. Methods Eighty patients with lung cancer were enrolled in this study, 34 of whom did not smoke and the others did. The expression of miR‐218 and CDK6 messenger RNA (mRNA) was measured using quantitative reverse transcription polymerase chain reaction (qRT‐PCR). A luciferase reporter system was used to identify the direct target of miR‐218. The protein expression of CDK6 was analyzed by using Western blotting. Cell proliferation was analyzed using an approach of calculation of cell number under a microscope. Results Nicotine decreased miR‐218 expression in non–small cell lung cancer (NSCLC) cells and promoted proliferation of NSCLC cells. Smoking patients with NSCLC had lower expression of miR‐218 in tumor compared with NSCLC patients who did not smoke. We found that miR‐218 directly targeted the CDK6 mRNA 3′untranslated region and inhibited its expression in NSCLC cells and also observed a negative correlation between the expression of miR‐218 and CDK6 mRNA in lung cancer tissues. Furthermore, miR‐218‐ or nicotine‐induced proliferative effects of NSCLC cells were rescued by the recovery of the expression level of CDK6. Conclusion Nicotine promotes proliferation of NSCLC cells through regulating the miR‐218/CDK6 axis, which may be a potential therapeutic target for lung cancer. 1. Nicotine can promote non–small cell lung cancer cell proliferation trough regulating the miR‐218/CDK6 axis. 2. The miR‐218/CDK6 axis may be a potential therapeutic target for non–small cell lung cancer.