Histone deacetylases (HDACs) inhibitor is a promising new approach to the treatment of lung cancer therapy via inhibiting cell growth and inducing apoptosis. miR-15a and miR-16-1 are important tumor suppressors through modulating B cell lymphoma 2 (Bcl-2), Cyclin D1, D2, and others.
Comparative modeling and docking studies of p16ink4/cyclin D1/Rb pathway genes in lung cancer revealed functionally interactive residue of RB1 and its functional partner E2F1.
At the overall analysis the CCND1 870A allele appeared to be associated with elevated lung cancer risk (for allele model, pooled OR=1.24, 95% CI: 1.08-1.44, P=0.004; for homozygous model, pooled OR=1.45, 95% CI: 1.14-1.84, P=0.003; for recessive model, pooled OR=1.29, 95% CI: 1.06-1.58, P=0.013; for dominant model, pooled OR=1.33, 95% CI: 1.08-1.65, P=0.009).
As expected, small interfering RNAs that reduced UBP43 expression also decreased cyclin D1 levels and increased apoptosis in a panel of lung cancer cell lines.
In conclusion, Rsf-1 is overexpressed in NSCLC and contributes to malignant cell growth by cyclin D1 and ERK modulation, which makes Rsf-1 a candidate therapeutic target in lung cancer.
Taken together, our results provided evidence that Interleukin-7/Interleukin-7 receptor induced cyclin D1 up-regulation via c-Fos/c-Jun pathway to promote proliferation of cells in lung cancer.
Meta-analyses of available data show a significant association between the CCND1G870A polymorphism and lung cancer risk, and CCND1G870A polymorphic variant A contributes to increased risk of lung cancer.
These results, along with closely related clinical results of the BATTLE program, support the promise of this cotargeting approach for lung cancer prevention and therapy and of cyclin D1 as a predictive, personalizing marker for it.
These findings support the conclusion that cell cycle regulation may play a role in lung cancer development and that CCND1rs9344 polymorphism together with smoking habit maybe a useful biomarker for lung cancer prediction.
Here we demonstrate that diazoxide inhibited the proliferation of lung cancer cells as well as the transcription of cell cycle-related protein Cyclin D1.
Compared with homozygous wild-types, the homozygous variant genotypes of STK15 F31I and CCND1G870A were associated with a significantly altered lung cancer risk with ORs of 0.58 (95% CI, 0.37-0.90) and 1.26 (95% CI, 1.03-1.53), respectively.
Therefore, we hypothesized that the genetic variants in these three genes influence the predisposition of lung cancer (i.e., CCND1G870A, CDKN2A Ala(148)Thr, TP53 Arg(72)Pro, and 16-bp repeat in intron 3) and that the effect of X-ray on lung cancer risk can be modified by the presence of these genetic variations.
In conclusion, it is suggested that the CCND1 G/A polymorphism is associated with the early onset of lung cancer in men and contributes to susceptibility to lung cancer, especially squamous cell cancer, in this population.
These and other pre-clinical and clinical studies that will be reviewed here indicate that cyclin D1 and perhaps other cyclins are attractive pharmacological targets for lung cancer chemoprevention.
A common A/G single nucleotide polymorphism (A870G) in exon 4 of the cyclin D1 gene, CCND1, is associated with the presence of 2 distinct mRNA transcripts for this G1/S regulatory protein, and CCND1 genotype has been related to prognosis in lung cancer and head and neck carcinoma.