ABSTRACT
Antioxidants are involved in the process of cellular damage prevention, which is considered as an avenue for cancer development. Free radicals are produced in the body upon exposure to stress, cigarette smoke, alcohol, toxins found in personal care products, pesticides in foods, radiation from the sun, viruses, germs or fungi etc. CCND1/CyclinD1 protein was found to be overexpressed in Oral squamous cell carcinoma. One hundred patients with oral squamous cell carcinoma were recruited along with hundred controls for this study from MNJ institute of Oncology with the approval of Ethics Committee, 5 ml blood samples were collected from each patient and centrifuged to collect serum for various assays. The antioxidant enzymes like catalase, SOD, GPX and GST were estimated using enzymatic assays. Results were expressed as unit of activity for mg of protein. Insilco analysis is performed using STRING v 11 Protein interaction tool. The patients with oral cancer had significantly reduced activities of SOD, GST and GPX (1.49 ± 0.49, 3.97 ± 0.86 and 10.7 ± 0.73 respectively) compared to healthy controls (4.37 ± 1.43, 6.10 ± 1.12 and 13.8 ± 1.25 respectively) (p < 0.005). However no significant difference was observed with regard to catalase activity (2.71 ± 6.51 and 4.03 ± 1.48) (p = 0.28). The proteins interaction PPI enrichment p-value was found to be 3.22e-10 predicted significantly more interactions. Our research findings shown that there was a decline in activity of superoxide dismutase, glutathione peroxidase and glutathione s transferase in addition, personal habits like smoking play a major role in the development and progression of oral carcinogenesis and based on Insilco analysis results CCND1/Cyclin D1 could be the potential therapeutic target in oral squamous cell carcinoma.
ABSTRACT
Phosphatase and tensin homolog (PTEN) and p16INK4a (p16) genes are tumor suppressor genes, associated with epigenetic alterations. PTEN and p16 promoter hypermethylation is a major epigenetic silencing mechanism leading to cancer. The cooperation between PTEN and p16 in pathogenesis of cancers suggest that their combination might be considered as potential molecular marker for specific subgroups of patients. Hence, the present study aimed to investigate whether PTEN and p16 promoter methylations were involved in oral squamous cell carcinoma (OSCC) in south Indian subjects. DNA methylation quantitative analyses of the two candidate tumor suppressor genes PTEN and p16 were performed by methylation-specific polymerase chain reaction (MSP). Fifty OSCC biopsy samples and their corresponding non-malignant portions as controls were studied comparatively. The methylation status was correlated with the clinical manifestations. Twelve out of 50 patients (24 %) were found to be methylated for PTEN gene, whereas methylation of the p16 gene occurred in 19 out of 50 cases (38 %). A statistically significant result was obtained (P = <0.0001 and 0.017) for both PTEN and p16 genes. PTEN and p16 promoter methylation may be the main mechanism leading to the low expression of PTEN and p16 genes indicating the progress of tumor development. Our data suggest that a low PTEN and p16 expression due to methylation may contribute to the cancer progression and could be useful for prognosis of OSCC. Therefore, analysis of promoter methylation in such genes may provide a biomarker valuable for early detection of oral cancer.
Subject(s)
Carcinoma, Squamous Cell/genetics , DNA Methylation , DNA, Neoplasm/genetics , Gene Expression Regulation, Neoplastic , Genes, p16 , Mouth Neoplasms/genetics , PTEN Phosphohydrolase/genetics , Adult , Aged , Biomarkers, Tumor , Biopsy , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/pathology , Cell Transformation, Neoplastic , Cyclin-Dependent Kinase Inhibitor p16/analysis , Cyclin-Dependent Kinase Inhibitor p16/physiology , DNA, Neoplasm/chemistry , Early Detection of Cancer , Female , Humans , India/epidemiology , Male , Middle Aged , Models, Biological , Mouth Neoplasms/epidemiology , Mouth Neoplasms/pathology , PTEN Phosphohydrolase/analysis , PTEN Phosphohydrolase/physiology , Promoter Regions, Genetic/genetics , Risk FactorsABSTRACT
BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNA molecules, implicated in several activities like initiation, progression and prognosis of various cancers. Single nucleotide polymorphisms (SNPs) in miRNA genes can lead to alteration in mRNA expression, resulting in diverse functional consequences. The aim of our study was to investigate the association of miR-149C>T and miR-196a2C>T SNPs with susceptibility to development of oral squamous cell carcinoma (OSCC) in South Indian subjects. MATERIALS AND METHODS: 100 OSCC patients and 102 healthy controls from the general population were recruited for the study. Genetic analysis was performed by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) as per a standard protocol. RESULTS: The genotype frequencies in miR-196a2 polymorphism, of TT, CT and CC in the OSCC patients were 69%,10% and 22% respectively while for control group it was 80%, 15% and 5% respectively. The CC genotype of miR196a2 polymorphism was significantly associated with oral squamous cell carcinoma. The genotype frequencies in miR-149 polymorphisms of CC, CT and TT in the oral squamous cell carcinoma (OSCC) patients were 72%, 22% and 6% respectively and for control group 88%, 12% and 0% respectively. CT and TT genotypes of miR149 polymorphism were found to be significantly associated with OSCC (p = 0.05 and 0.07). CONCLUSIONS: Our study suggests that miR-196a2C>T and miR-149C>T polymorphisms may play crucial roles in the development of OSCC in South Indian subjects.
