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

Abstract

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.

Genetic variants of CHEK1, PRIM2 and CDK6 in the mitotic phase‐related pathway are associated with nonsmall cell lung cancer survival

“…42 Similarly, the nicotine-induced proliferative effects were rescued by the recovery of the expression levels of CDK6 in NSCLC. 43 These findings also indicated that CDK6 might also have an oncogenic role in NSCLC, which is consistent with our results that the expression of CDK6 was increased in lung cancer tissues than in the paired adjacent normal tissues, especially in the LUSC, and that higher expression of CDK6 was associated with a worse survival of patients with NSCLC. Furthermore, the CDK6 rs113181986 C allele was correlated with decreased mRNA expression of CDK6 and a better outcome in patients with NSCLC, which supports the biological plausibility of the findings.…”

“…It was previously reported that LncRNA associated with poor prognosis of hepatocellular carcinoma could accelerate the progression of NSCLC by upregulating CDK6 42 . Similarly, the nicotine‐induced proliferative effects were rescued by the recovery of the expression levels of CDK6 in NSCLC 43 . These findings also indicated that CDK6 might also have an oncogenic role in NSCLC, which is consistent with our results that the expression of CDK6 was increased in lung cancer tissues than in the paired adjacent normal tissues, especially in the LUSC, and that higher expression of CDK6 was associated with a worse survival of patients with NSCLC.…”

Effects and mechanism of microRNA‑218 against lung cancer

“…mir, microrna; nSclc, non-small cell lung cancer; PTen, antiphosphatase and tensin homolog; BMi-1, anti-polycomb complex protein BMi-1; YY1, anti-transcriptional repressor protein YY1; VeGF, vascular endothelial growth factor. which was consistent with other studies (32,34,41). The effect of mir-218 on cell cycle progression was further investigated using flow cytometry.…”

“…as a tumor-suppressor mirna, mirna (mir)-218 is downregulated in tumor progression and is associated with prognosis in nSclc (30)(31)(32). Furthermore, mir-218 can participate in tumor progression by regulating target genes including PXN, IL6R, JAK3, SLUG, ZEB2, EGFR, MEF2D, CDCP1, RUNX2, HMGB1, ETK, HOXA1, CDK6 and ROBO1 (31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42). The present study revealed for the first time, to the best of the authors' knowledge, the expression levels and therapeutic potential of mir-218 in XWlc-05.…”

Role of miR‐218‐GREM1 axis in epithelial‐mesenchymal transition of oral squamous cell carcinoma: An in vivo and vitro study based on microarray data

“…After subsequently culturing the cells in a complete culture medium for 24‐48 hours, the cells were collected, and their RNA and protein were extracted for analysis. The primer sequence for miR‐218 mimic was: 5′UUGUGCU UGAUCUAACCAUGU3′, 21 and that for miR‐218 inhibitor was: 5′AACACGA ACUAGAUUGGUACA3′.…”