hsa-miR-423 rs6505162 Is Associated with The Increased Risk of Breast Cancer in Isfahan Central Province of Iran.

OBJECTIVE: Thirteen million cancer deaths and 21.7 million new cancer cases are expected in the world by 2030. Breast cancer is considered as the main cause of cancer mortality in women aged 20-59 years. microRNAs (miRNAs) regulate gene expression at the post-transcriptional level and they are highly expressed in malignancies, including breast cancer. The role of miRNAs in the pathogenesis of breast cancer is not fully understood. In the present study, for the first time, the impact of hsa-miR-423 rs6505162 on breast cancer risk was investigated in the central province of Iran, Isfahan. MATERIALS AND METHODS: This case-control study was conducted on 153 clinicopathological proven breast cancer patients and 153 sex-matched healthy women with no history of any cancer type and relative patients. The patients and controls were genotyped and association of their clinical characteristics with hsa-miR-423 rs6505162 genotype was analyzed. RESULTS: The findings indicated that CC genotype of hsa-miR-423 rs6505162 was associated with the increased risk of breast cancer [odds ratio (OR)=2.37, 95% confidence interval (CI)=1.29-4.35 and P=0.0023, CC vs. AA]. CONCLUSION: The data suggested that hsa-miR-423 rs6505162 could be considered as a novel risk factor in breast cancer pathogenesis in Isfahan province of Iran.

Evaluation of Tumor Regulatory Genes and Apoptotic Pathways in The Cytotoxic Effect of Cytochalasin H on Malignant Human Glioma Cell Line (U87MG).

OBJECTIVE: The aim of current study was to provide a proof-of-concept on the mechanism of PLAU and PCDH10 gene expressions and caspases-3, -8, and -9 activities in the apoptotic pathway after treatment of malignant human glioma cell line (U87MG) with cytochalasin H. MATERIALS AND METHODS: In the present experimental study, we have examined cytochalasin H cytotoxic activities as a new therapeutic agent on U87MG cells in vitro for the first time. The cells were cultured and treated with 10-5-10-9 M of cytochalasin H for 24, 48 and 72 hours. The assessment of cell viability was carried out by (3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazoliumbromide (MTT) assay at 578 nm. The data are the average of three independent tests. mRNA expression changes of PLAU and PCDH10 were then evaluated by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). The fluorometric of caspases-3, -8, and -9 activities were carried out. The morphology changes in the U87MG cells were observed by fluorescence microscope. RESULTS: MTT assay showed that cytochalasin H (10-5 M) inhibited the U87MG cancer cells proliferation after 48 hours. Analysis of qRT-PCR showed that the PLAU expression was significantly decreased in comparison with the control (P<0.05). The expression of PCDH10 also showed a significant increase when compared to the control (P<0.001). Fluorescence microscope indicated morphological changes due to apoptosis in U87MG cancer cells, after treatment with cytochalasin H (10-5 M, 48 hours). The fluorometric evaluation of caspase-3, -8, and -9 activities showed no significant difference between the caspases and the control group. CONCLUSION: This study shows the effect of caspase-independent pathways of the programmed cell death on the U87MG cancer cell line under cytochalasin H treatment. Further studies are needed to explore the exact mechanism.

Epidermal growth factor receptor gene expression evaluation in colorectal cancer patients.

Background: Colorectal cancer is one of the most common causes of death in the world and third and fourth most common cancer among men and women in Iran respectively. Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor that shows over expression in epithelial tumors and regulates important processes in tumorigenesis. Incidence and characteristics of colorectal cancer are based on the geographic region and race. Aim: In this research work, the over expression of EGFR in formalin fixed paraffin-embedded (FFPE) colorectal cancer tumor tissue of patients was studied. Materials and Methods: Fifteen FFPE colorectal cancer tumor tissues (10 women and 5 men; 25-65 years old and stage IV) and 15 non-patients (nine women and six men; 25-65 years old) that were collected during 2006-2012. EGFR gene expression level was analyzed by real-time quantitative reverse transcriptase polymerase chain reaction (PCR). All PCR reactions were performed in triplicate for both target gene and internal control (18s ribosomal ribonucleic acid) with the 2-ΔΔCT method. Gene expression differences in patients and controls were evaluated with t-test. Results: The results were showed EGFR gene over expression in 12 (80%) of 15 patients. There was a statistically significant difference in the prevalence of EGFR expression between patients and control (P < 0.05). Conclusion: Our results demonstrated EGFR gene over expression in colorectal cancer tumor tissue compared with controls.