Downregulation of MiR-218 by Nicotine Promotes Cell Proliferation Through Targeting CDK6 in Non-small Cell Lung Cancer

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.