Search

Tumor relapse is the main cause of breast cancer related deaths and metastasis due to epithelial–mesenchymal transition (EMT) having a critical role in this process. MAML1 is the main co activator of NOTCH signaling pathway and its role in EMT remains unknown. In this study, this role was evaluated through overexpression and knockdown study of MAML1 in MCF7 and MDA-MB-231 cells. MAML1 overexpression up regulated the epithelial and down regulated the mesenchymal markers. In addition, MAML1 silencing decreased epithelial and increased mesenchymal markers. Notch inhibition using γ-secretase inhibitor resulted in increased E-cadherin expression. MAML1 ectopic expression, further increased E-cadherin expression with inhibition of NOTCH signaling. Wound healing assay showed that MAML1 overexpression decreases the rate of migration, while MAML1 silencing increases this rate significantly. In conclusion, our data indicated that MAML1 negatively regulates EMT markers expression in breast cancer cells.

Objective Intrauterine growth restriction (IUGR) is one of the most important causes of the fetus and newborn mortality in the population. The aim of this study was to investigate the relationship between hTERT gene expression level and IUGR pregnancy in an Iranian population. Study design The hTERT expression was analyzed in 66 placenta samples consisting of 33 controls and 33 IUGRs, and compared by Real-Time Polymerase Chain Reaction (PCR). The results were statistically analyzed using SPSS software. Results There was no significant difference between the placentas samples of IUGR and healthy individuals for hTERT gene expression (p = 0.621). Conclusions To the best of our knowledge, the current investigation is the first study on the association between hTERT gene expression and IUGR in Iran. According to our results, there was no significant correlation between hTERT and IUGR etiology in this study. Surely, using more samples could provide more definite results on this matter in the future.

Background Pterygium is the human eye lesion whose prevalence in the general population is estimated about 2%. The disease, in extreme phase, can lead to visual disturbance and eventually causes complete loss of vision due to the lesion growth over the papillary axis. Pterygium invasive tissue is a tumor-like tissue that is initially identified and then is attacked by cytotoxic T cells. Cytotoxic T lymphocyte associated antigen 4 (CTLA4), as a modulator molecule of the adaptive immune system, plays a critical role in maintaining peripheral T cell tolerance by diminishing its responsiveness and increasing its activation threshold. The aim of this study is to investigate the association between some epigenetic changes of the CTLA4 gene, such as promoter methylation and gene expression, and pathogenesis of pterygia. Materials and methods Genomic DNA was extracted from 75 formalin-fixed, paraffin-embedded tissues of pterygia and 70 specimens of normal conjunctiva from eyes without pterygium as the control group, collected from Sistan and Baluchestan population. CTLA4 gene promoter methylation was carried out by methylation-specific PCR technique. The gene expression analysis was done on extracted total RNA from 20 healthy and 23 pterygium tissue samples using Real-Time PCR technique. Results Promoter methylation changes of CTLA4 gene were not statistically different in patients with pterygium in comparison with healthy controls (OR = 1.614; 95% CI = 0.57–4.75; P value = 0.37). However, gene expression level of CTLA4 was remarkably different in patients and healthy controls (Mean ± SD: 1.343 ± 0.133 and 2.027 ± 0.219, respectively; P value = 0.009). Conclusion This is a credible evidence of CTLA4 gene expression in human eye tissue. This first hand attempt of investigating the association of epigenetic changes of the CTLA4 gene and pathogenesis of pterygia, indicated a significant intensification of the gene expression of CTLA4 in patients with pterygia. We suggest that increasing CTLA4 gene expression can be a trigger which promotes pterygium enlargement. However, further studies on more populations with larger sample sizes need to be done to verify this hypothesis in the future.

In addition to other factors regarding the disease susceptibility, genetic factors are the main causes of Hashimoto's thyroiditis (HT) disease. CTLA4 and PTPN22 are the most prominent genes involved in the immune system regulation, thus effective in the pathogenesis of autoimmune diseases. In the current study, the association of two polymorphisms of CTLA4 and PTPN22 genes, 1661A/G (CTLA-4 gene) and C1858T (PTPN22 gene), with HT was investigated by PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) technique. The effects of -1661A/G and C1858T polymorphisms on the mRNA and protein structures of CTLA-4 and PTPN22 were investigated by an in silico analysis. There was no significant difference between the genotype and allele frequencies of PTPN-22 gene polymorphism (rs2476601) in case and control groups. There was a positive association between the frequency of heterozygous genotype of CTLA4-1661A/G polymorphism (rs4553808) and HT (P = .04), but no association was seen regarding allele frequencies. In-silico analysis predicted that the transition of allele A to allele G would lead to the loss of some of the binding sites. Also, the structural analysis of C1858T transition effect on protein revealed a significant influence on PTPN-22 function. Our results showed that heterozygous genotype of -1661A/G CTLA4 gene variation might be related with the risk of HT.

Background Oral cancer represents the third most prevalent form of malignancy in the developing countries and the eight most common form of cancer in developed countries. Alcohol and tobacco users are most affected by oral cancers and 90% of them are OSCC in adult males. In some provinces in Iran such as, Sistan and Baluchestan its prevalence is higher compared to other provinces. One of the primary neurotransmitter in the central nervous system is systemic glutamate, which is a major excitatory neurotransmitter. Glutamate signaling has been involved in various non-neuronal cancer processes. The aim of this research was to highlight the association between DNA methylation of the glutamate receptor genes and their expression pattern in pathogenesis of OSCC. Materials and methods Genomic DNA was isolated from 83 OSCC paraffin-embedded tissues (mean age: 59.67 ± 16.08) and 80 normal samples (mean age: 50.15 ± 16.69). Promoter methylation status of glutamate receptors including GRM5, GRM2 and GRIA3 genes were carried out by Methylation Specific PCR technique (MSP). We also investigated the mRNA expression levels of these genes, in 15 paraffin-embedded patients and healthy samples using real-time PCR techniques. Result DNA methylation analysis showed statistically significant differences in the cases in comparison with healthy controls. Our data showed that the promoters of GRM2 and GRIA3 were methylated in the cases. For GRM2 (MM: OR = 0.32; 95% CI = 0.02–3.90; p-value = .37; MU: OR = 8.0; 95% CI = 1.37–47.34; p-value = .02) and GRIA3 (MM: OR = 47.19; 95% CI = 4.61–483.0; p-value = .001; MU: OR = 1.45; 95% CI = 0.35–5.89; p-value = .6). However, methylation of GRM5 promoter was not statistically different between cases and healthy controls, GRM5 (MM: OR = 0.9; 95% CI = 0.14–5.71; p-value = .9; MU: OR = 1.83; 95% CI = 0.33–10.09; p-value = .4). In addition, the evaluation of mRNA expression levels of GRM2, GRIA3 and GRM5 were remarkably different in the cases and healthy controls (p

Summary Reactive oxygen species can affect many cellular functions through protein oxidation or initiation of the lipid peroxidation cascade that can lead to non-alcoholic fatty liver disease (NAFLD), characterized by significant lipid deposition in the hepatocytes of patients with no history of excess alcohol intakes. The present study aimed to analyze the methylation status of the antioxidative stress genes GSTT1 (glutathione S-transferase theta-1) and GSTP1 (glutathione S-transferase pi-1), and their expression profiles, in a sample population of patients with NAFLD living in South-East Iran. Patients and methods Peripheral blood samples were obtained from 80 NAFLD patients and 80 healthy controls. Promoter methylation of the GSTT1 and GSTP1 genes were analyzed by methylation-specific polymerase chain reaction (MS-PCR). Expression profiles of these genes were also examined by quantitative real-time PCR analysis. Results Promoter methylation of the GSTT1 gene was detected in 86.2% of cases and in 91.2% of controls and, of the GSTP1 gene, in 88.8 and 87.5% of cases and controls, respectively. Promoter methylation of GSTT1 and GSTP1 was not statistically different in cases compared with healthy controls. Similarly, mRNA expression levels showed no statistically significant variations between healthy individuals and patients with NAFLD. Conclusion Our findings indicate no association between methylation status and expression profiles of GSTT1 and GSTP1 genes and NAFLD. This is the first report to assess such associations in a sample of the Iranian population.

Background Several genetic alterations have been reported to contribute to the development of oral squamous cell carcinoma (OSCC). Methylation of CpG-islands in cancer-related genes may serve as epigenetic biomarkers for oral cancer diagnosis and prognosis. The objective of this study was to analyze methylation profile of MGMT and CDH1 genes and their link with expression activity in patients with oral cavity cancer. Methods Promoter hypermethylation status of MGMT and CDH1 genes were assayed by Methylation-specific PCR (MSP) in OSCC ( n = 76) tissues kept in paraffin and normal oral tissues ( n = 57) served as control. Also, we investigated MGMT and CDH1 mRNA levels by real-time quantities reverse transcripts PCR. Methylation and mRNA expression profiles of these genes and their association with clinical data were determined. Results Aberrant promoter hypermethylation of CDH1 and MGMT genes were detected in 61.8% (47 of 76) and 73.7% (56 of 76) of the OSCC cases, respectively, with significant difference between cases and controls for MGMT ( P = 0.027). CDH1 promoter methylation in cases and healthy controls was not significant. The mRNA expression level results showed statistically significant ( P = 0.03) differences between cases and healty controls for the MGMT gene. However, the difference for the CDH1 gene was not significant. Conclusion Our findings, for the first time, in a South-Eastern Iranian population, indicate that the two genes are aberrantly methylated in OSCC, and that MGMT methylation may be considered as a potential molecular marker for the poor survival in advanced OSCC.