In accordance with the developmental mode of lung cancer established by Sekine et al., we assumed that the occurrence and development of lung cancer were linked not only to gene loss in the 3p region (WNT7A, 3p25) and genetic mutations in the 9p region but also to similar events in the regions of 1p36.2 (FRAP1), 6q25.2-q27 (PARK2), and 11q13 (CCND1).
Together, our results suggest that PMLIV interacts with nEGFR upon EGFR activation and represses the transcription of nEGFR target genes such as CCND1 and thus leading to inhibition of the lung cancer cell growth.
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.
Sub-group analysis revealed that high expression of cyclin D1 was related to worse OS of head and neck cancers (HR=2.08, 95% CI: 1.75-2.47; P<0.001), but not in breast (HR=1.033, 95% CI: 0.873-1.223, P= 0.702), gastrointestinal (HR = 1.025, 95% CI:0.824-1.275; P=0.825), bladder (HR=0.937, CI: 0.844-1.041; P=0.225) and in lung cancer patients (HR=1.092, CI: 0.819-1.455; P=0.549).
These results indicate that ARMC8α upregulates cyclin D1 and MMP7 expression by activating the canonical Wnt-signaling pathway and thereby promoting lung cancer cell proliferation and invasion.
These effects may result from the ability of miR-5100 to promote G1/S transition and downregulate cyclin D1 and cyclin-dependent kinases 2 (CDK2) expressions in lung cancer stable cells.
The impact of miRNA-21 on the expression of cyclin D1, caspase-3, and matrix metalloprotease-9 (MMP9) was also studied. miRNA-21 expression was significantly higher in lung cancer cell lines (A549, HCC827, NCI-H282, and 95-D) than that in normal human bronchial epithelial cells (HBE; p < 0.05).
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.
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.
Our meta-analysis indicated that CCND1G870A genetic polymorphism was a risk factor for lung cancer under homozygote model (OR = 1.18; 95% CI = 1.02, 1.37), recessive model (OR = 1.21; 95% CI = 1.03, 1.41), and allele model (OR = 1.11; 95% CI = 1.02, 1.21).
Mechanistically, we show that inhibition of mTOR potentiates WEE1 inhibition by abrogating compensatory activation of DNA repair, exacerbating DNA damage in <i>KRAS</i>-mutant NSCLC, and that this effect is due in part to reduction in cyclin D1.<b>Conclusions:</b> These findings demonstrate that compromised DNA repair underlies the observed potent synergy of WEE1 and mTOR inhibition and support clinical evaluation of this dual therapy for patients with <i>KRAS</i>-mutant lung cancers.<i></i>.
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.
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.
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.
This study was carried out to examine cyclin D1 (CCND1) and retinoblastoma (RB1) gene expression in the bronchial epithelium of patients with lung cancer.