The conclusion that we derive from this study is that Skp2 regulates colorectal cancer cell growth by inhibiting the expression of cell cycle regulator p27 and p16.
The authors analyzed v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) codon 12 mutations, the v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) thymine to adenine substitution at codon 1788, and tumor protein 53 (p53) mutations and investigated promoter methylation of Ras association (RalGDS/AF-6) domain family member 1 protein (RASSF1a), E-cadherin, and cyclin-dependent kinase inhibitor 2A (p16INK4a) in 101 primary CRCs (67 stage III and 34 stage IV) and related lymph node and liver metastases.
We found that CD44(+)/aldehyde dehydrogenase (ALDH)(+) slowly proliferating immature CRC stem cell populations expressed relatively low levels of JARID1B and the differentiation marker, CD20, as well as relatively high levels of the tumor suppressor, p16/INK4A.
In conclusion, concurrent methylation of NEUROG1 and CDKN2A (p16) is associated with recurrence following adjuvant FOLFOX in Stages II/III colorectal cancer.
Furthermore, there was a significant association between CDKN2A hypermethylation and lymphovascular invasion (OR 1.68, 95% CI 1.15-2.47), lymph node metastasis (OR 1.68, 95% CI 1.09-2.59) and proximal tumour location (OR 2.09, 95% CI 1.34-3.26) of colorectal cancer.
Therefore, the polymorphisms of p16 540 C>G, 580 C>T, and MDM2 SNP309 T>G designed to investigate the risk of CRC development and progression in a Turkish population.
Additionally, in the analysis of the studies following REMARK guidelines more rigorously, p16 hypermethylation had unfavorable impact on OS of NSCLC (HR 1.79, 95% CI: 1.35-2.39) and CRC (HR 1.96, 1.16-3.34), and on DFS of NSCLC (HR 2.12, 95% CI: 1.21-3.72) and head and neck cancer (HR 2.24, 95% CI: 1.35-3.73).
Considering tumors with telomere shortening, expression for BNIP3, DAPK1, NDRG1, EGFR, and CDKN2A was significantly higher in NSCLC than in CRC, whereas TP53 was overexpressed in CRC with respect to NSCLC.
We aimed to determine the possible role of miRNA-binding site polymorphisms located in five cancer-related genes: IL-16, CDKN2A (p16), RAF1, PTGER4, and ITGB4 in colorectal cancer (CRC) risk modification in an Iranian population.
Additionally, the effects of lentiviral-mediated RNA interference (RNAi) of UHRF1 on cell proliferation and migration, cell cycle and apoptosis, and the expression of p16(ink4a) and p21(waf1/cip1) were investigated in CRC cell lines.
p16(INK4a) MS could sensitively reflect the recurrence status and may be useful for identifying the presence of recurrence during the follow-up of CRC patients.
The present study was conducted to examine whether the methylation profile of p16INK4a and hMLH1 (human mutL homologue 1) promoters was associated with clinical features and patients' survival in CRC (colorectal carcinoma).
Despite its well-established role in carcinogenesis, CDKN2A (p16) promoter methylation or loss of expression in colorectal cancer is not independently associated with patient prognosis.
Therefore, our data provide evidence for oncogene-induced senescence in the serrated route to colorectal cancer with BRAF mutation and upregulation of p16(Ink4a) expression appears to be a useful indicator of induction of senescence.
Of 151 paraffin-embedded CRC tissue samples, 51 (34%), 54 (36%), and 46 (30%) were classified as low, intermediate, and high for aberrant methylation of p16((INK4a)).
We evaluated the implication of USP22 and the candidate targets, such as B-cell-specific murine leukemia virus integration site-1 (BMI-1), cellular homolog of avian myelocytomatosis virus oncogene (c-Myc), cyclin D2, inhibitor of cyclin-dependent kinase (CDK) 4 (p16INK4a), and an alternate reading frame product of the CDKN2A locus (p14ARF), in matched samples comprising carcinoma and adjacent non-cancerous mucosa from 82 patients with CRC using quantitative reverse transcription-polymerase chain reaction and immunostaining analyses.
The detection limit of IP-MSP for p16 methylation was determined with a standard made by cell line (SKCO-1) lysate. p16 methylation of tumor and/or serum of 51 colorectal cancers and 10 adenoma patients, and 10 healthy volunteers was detected with conventional MSP or IP-MSP.
In colorectal carcinomas, expression of the p16(INK4A) gene is regulated by beta-catenin/TCF4 and correlates with low survival rates of patients with tumors displaying an infiltrative front of invasion.
Aberrant methylation of the p16 gene was detected in 20 out of the 50 (40%) primary colon carcinomas, suggesting that the aberrant methylation of p16 was frequently observed in colorectal carcinomas.
The results suggest that disruption of the p53/MDM2/p14ARF pathway may frequently participate in colonic carcinogenesis and that MDM2 expression status may be a factor in the prediction of potential invasion and liver metastasis of colorectal carcinomas.