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Breast cancer is a major cause of cancer-related death in women worldwide. miRNAs are new players of breast tumorigenesis, used as diagnostic and prognostic biomarkers. Among various miRNAs, miR-126 has been proposed to have a tumor suppressive role in HER2 positive cancer. However, to have a better understanding of its role, further validation is required. The aim of this study was evaluating miR-126 expression level in breast cancer tissues and investigating its potential association with HER2, estrogen and progesterone receptors. miR-126 expression level was measured in 108 specimens including 78 malignant and 30 normal samples using RT-qPCR. The outcome was statistically analyzed. In silico studies were performed to find the potential mechanism of action, through which miR-126 imposes its function. Down-regulation of miR-126 was observed in tumor samples, as compared to the matched normal tissues. Down-regulation of miR-126 was also associated significantly with the absence of estrogen receptor in malignant samples. No association between miR-126 expression and HER2 status was observed. Our in silico analyses showed the possible role of Crk, PI3K and Ras proto-oncogenes in breast cancer tumorigenesis. miR-126 is significantly down-regulated in breast cancer tissues. Statistically, it showed no correlation with HER2 positivity. However, the association between lower miR-126 and estrogen receptor negativity was observed.
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OBJECTIVES: For the first time, we used molecular signaling pathway enrichment analysis to determine possible involvement of miR-126 and IRS-1 in neurotrophin pathway. MATERIALS AND METHODS: In this prospective study, Validated and predicted targets (targetome) of miR-126 were collected following searching miRtarbase (http://mirtarbase.mbc.nctu.edu.tw/) and miRWalk 2.0 databases, respectively. Then, approximate expression of miR-126 targeting in Glioma tissue was examined using UniGene database (http://www.ncbi. nlm.nih.gov/unigene). In silico molecular pathway enrichment analysis was carried out by DAVID 6.7 database (http://david. abcc.ncifcrf.gov/) to explore which signaling pathway is related to miR-126 targeting and how miR-126 attributes to glioma development. RESULTS: MiR-126 exerts a variety of functions in cancer pathogenesis via suppression of expression of target gene including PI3K, KRAS, EGFL7, IRS-1 and VEGF. Our bioinformatic studies implementing DAVID database, showed the involvement of miR-126 target genes in several signaling pathways including cancer pathogenesis, neurotrophin functions, Glioma formation, insulin function, focal adhesion production, chemokine synthesis and secretion and regulation of the actin cytoskeleton. CONCLUSIONS: Taken together, we concluded that miR-126 enhances the formation of glioma cancer stem cell probably via down regulation of IRS-1 in neurotrophin signaling pathway.
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INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) ranks among nephrotic syndromes. Research shows that FSGS is brought about by several genes including transient receptor potential cation channel subfamily c member 6 (TRPC6). This study aimed to investigate TRPC6 gene in Iranian FSGS children. MATERIALS AND METHODS: Twenty-six FSGS patients were included. They were all under 16 years old. Polymerase chain reaction amplification and sequencing were performed to examine exons 2 and 13 of TRPC6 gene. RESULTS: Sampling was performed when the patients had a mean age of 9.26 ± 3.19 years. Sixteen children were boys (61.5%); male-female ratio was 1.35:1. Four patients (15.4%) were diagnosed with TRPC6 variants. Three missense nonsynonymous mutations (C121S, D130V, and G162R) and 1 synonymous mutation (I111I) were detected. All variants were novel; in silico analysis predicted D130V and G162R as pathogenic. Patients with and without mutations were not different significantly regarding age at disease onset, sex, consanguinity, hypertension, hematuria, serum creatinine and albumin, rate of progression to kidney failure, response to steroids, and resistance to cyclosporine A and cyclophosphamide. CONCLUSIONS: This study examined exons 2 and 13 of TRPC6 gene in Iranian FSGS children. Four novel TRPC6 variants were detected; in silico analysis showed that 2 variants (D130V and G162R) could be pathogenic. It could be concluded that TRPC6 may be useful for genetic screening in Iranian FSGS children.
