Tabriz University of Medical Sciences

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  • Squamous cell carcinoma of esophagus (SCCE) occurs at a high incidence rate in certain parts of the world. This feature necessitates that different aspects of the disease and in particular genetic cha...racteristics be investigated in such regions. In addition, such investigations might lead to achievement of molecular markers helpful for early detection, successful treatment and follow up of the disease. Adenomatous Polyposis Coli (APC) promoter hypermethylation has been shown to be a suitable marker for both serum and solid tumors of adenocarcinoma of esophagus. We investigated the status of APC promoter hypermethylation in Iranian patients, compared the results with the former studies, and evaluated its applicability as a candidate molecular marker by examining association between survival of SCCE patients and APC promoter methylation.Show more
    Zare M,Jazii FR,Alivand MR,Nasseri NK,Malekzadeh R,Yazdanbod M
    BMC cancer
  • To survey the changes of promoter CpG methylation status and mRNA expression of IL17RC (interleukin 17 receptor C) gene in retinal pigment epithelium (RPE) cells under chemical hypoxia condition for c...horoidal neovascularization (CNV) modeling in vitro.Show more
    Alivand MR,Sabouni F,Soheili ZS
    Current eye research
  • CpG methylation of DNA takes part in a specific epigenetic memory that plays crucial roles in the differentiation and abnormality of the cells. The methylation pattern aberration of genomes is affecte...d in three ways, namely DNA methyltransferase(DNMT), Ten-eleven translocation(TET), and methyl-binding Domain(MBD) proteins. Of these, TET enzymes have recently been demonstrated to be master modifier enzymes in the DNA methylation process. Additionally, recent studies emphasize that not only do epigenetic phenomena play a role in controlling hypoxia pathway, but the hypoxia condition also triggers hypomethylation of genomes that may help with the expression of hypoxia pathway genes. In this study, we suggested that TET1 and TET2 could play a role in the demethylation of genomes under chemical hypoxia conditions. Herein, the evaluating methylation status and mRNA expression of mentioned genes were utilized through real-time PCR and methylation-specific PCR (MSP), respectively. Our results showed that TET1 and TET2 genes were overexpressed (p< 0.05) under chemical hypoxia conditions in Retinal Pigment Epithelial(RPE)cells, whereas the promoter methylation status of them were hypomethylated in the same condition. Therefore, chemical hypoxia not only causes overexpression of TET1 and TET2 but also could gradually do promoter demethylation of same genes. This is the first study to show the relationship between epigenetics and the expression of mentioned genes related to hypoxia pathways. Furthermore, it seems that these associations in RPE cells are subjected to chemical hypoxia as a mechanism that could play a crucial role in methylation pattern changes of hypoxia-related diseases such as cancer and ischemia. This article is protected by copyright. All rights reserved.Show more
    Alivand MR,Soheili ZS,Pornour M,Solali S,Sabouni F
    Journal of cellular biochemistry
  • In recent years, genome-wide association studies (GWAS) have made great progress in elucidating the genetic influence on complex traits. An overwhelming number of GWAS signals resides in regulatory el...ements, therefore most post-GWAS studies focused only on transcriptional regulatory variants. However, recent findings have expanded the spectrum of trait/disease-associated regulatory variants beyond transcriptional level and highlighted the importance of post-transcriptional variants like those in miRNA targetome. The present work integrated genome-wide association data of coronary artery disease (CAD) with population-specific linkage disequilibrium structures from 1000 Genomes Project to map disease associations to miRNA targetome. Moreover, we performed a variety of functional prediction analyses to prioritize disease-associated variants (DAVs) influencing miRNA targetome and in-silico analyses to get insights into their functional significance. In conclusion, although the role of miRNA targetome variations in the development of CAD still has to be fully elucidated, we provided a systematic bioinformatics approach to the miRNA targetome variations in CAD. The results of this study will be valuable for researchers interested in the identification of CAD GWAS signals that may implicate polymorphic miRNA targeting.Show more
    Bastami M,Nariman-Saleh-Fam Z,Saadatian Z,Nariman-Saleh-Fam L,Omrani MD,Ghaderian SM,Masotti A
  • Esophageal cancer is the eighth most common cancer worldwide. Also middle-aged obese adults with higher body mass index during childhood have a greater risk to develop esophageal cancer. The contribut...ion of microRNAs to esophageal cancer has been extensively studied and it became clear that these noncoding RNAs may play crucial roles in pathogenesis, diagnosis and prognosis of the disease. Increasing evidences have suggested that polymorphisms perturbing microRNA targetome (i.e., the compendium of all microRNA target sites) are associated with cancers including esophageal cancer. However, the extent to which such variants contribute to esophageal cancer is still unclear. In this study, we applied an in silico approach to systematically identify polymorphisms perturbing microRNA targetome in esophageal cancer and performed various analyses to predict the functional consequences of the occurrence of these variants. The computational results were integrated to provide a prioritized list of the most potentially disrupting esophageal cancer-implicated microRNA targetome polymorphisms along with the in silico insight into the mechanisms with which such variations may modulate microRNA-mediated regulation. The results of this study will be valuable for future functional experiments aimed at dissecting the roles of microRNA targetome polymorphisms in the onset and progression of esophageal cancer.Show more
    Nariman-Saleh-Fam Z,Bastami M,Somi MH,Samadi N,Abbaszadegan MR,Behjati F,Ghaedi H,Tavakkoly-Bazzaz J,Masotti A
    Cell biochemistry and biophysics
  • Considering that MAPK (mitogen- activated protein kinase) signaling pathway has an important role in the progression of inflammatory cytokine secretion in type 2 diabetes mellitus (T2DM), we have rece...ntly investigated the reported genetic polymorphism from genome wide association study in MAP3K1 (mitogen-activated protein kinase kinase kinase 1) in diabetes as an important member of MAPK signaling. This study aimed to investigate the possible association of rs10461617 at the upstream of MAP3K1 gene in an Iranian case-control study with the risk of T2DM. The study population was comprised of 342 unrelated Iranian individuals including 177 patients with T2DM and 165 unrelated healthy control subjects. Genotyping was performed using PCR-RFLP and confirmed with sequencing. In a logistic regression analysis, the rs10461617A allele was associated with a significantly higher risk of T2DM assuming the log- additive model (OR: 1.44, 95% CI: 1.01-2.05, P = 0.039). In conclusion, we provided the first evidence for the association of rs10461617 at the upstream of MAP3K1 with the risk of T2DM in an Iranian population.Show more
    Torkamandi S,Bastami M,Ghaedi H,Moghadam F,Mirfakhraie R,Omrani MD
    International journal of molecular and cellular medicine
  • The present work is aimed at finding variants associated with Type 1 and Type 2 diabetes mellitus (DM) that reside in functionally validated miRNAs binding sites and that can have a functional role in... determining diabetes and related pathologies. Using bioinformatics analyses we obtained a database of validated polymorphic miRNA binding sites which has been intersected with genes related to DM or to variants associated and/or in linkage disequilibrium (LD) with it and is reported in genome-wide association studies (GWAS). The workflow we followed allowed us to find variants associated with DM that also reside in functional miRNA binding sites. These data have been demonstrated to have a functional role by impairing the functions of genes implicated in biological processes linked to DM. In conclusion, our work emphasized the importance of SNPs located in miRNA binding sites. The results discussed in this work may constitute the basis of further works aimed at finding functional candidates and variants affecting protein structure and function, transcription factor binding sites, and non-coding epigenetic variants, contributing to widen the knowledge about the pathogenesis of this important disease.Show more
    Ghaedi H,Bastami M,Jahani MM,Alipoor B,Tabasinezhad M,Ghaderi O,Nariman-Saleh-Fam Z,Mirfakhraie R,Movafagh A,Omrani MD,Masotti A
    Biochemical genetics
  • Recent studies have suggested that single-nucleotide polymorphisms (SNPs) in miRNA genes or their binding sites may alter an individuals susceptibility to coronary artery disease (CAD). In the present... study, the association between two such SNPs (rs2910164 in miR-146a and rs12190287, which disrupts miRNA binding to TCF21) and CAD, in an Iranian population, was evaluated and in silico analyses were conducted to predict disease-related effects of miR-146a rs2910164.Show more
    Bastami M,Ghaderian SM,Omrani MD,Mirfakhraie R,Vakili H,Parsa SA,Nariman-Saleh-Fam Z,Masotti A
    Genetic testing and molecular biomarkers
  • It has been suggested that single nucleotide polymorphisms (SNPs) in genes involved in Toll-like receptors (TLRs) pathway may exhibit broad effects on function of this network and might contribute to ...a range of human diseases. However, the extent to which these variations affect TLR signaling is not well understood. In this study, we adopted a bioinformatics approach to predict the consequences of SNPs in TLRs network. The consequences of non-synonymous coding SNPs (nsSNPs) were predicted by SIFT, PolyPhen, PANTHER, SNPs&GO, I-Mutant, ConSurf and NetSurf tools. Structural visualization of wild type and mutant protein was performed using the project HOPE and Swiss PDB viewer. The influence of 5-UTR and 3- UTR SNPs were analyzed by appropriate computational approaches. Nineteen nsSNPs in TLRs pathway genes were found to have deleterious consequences as predicted by the combination of different algorithms. Moreover, our results suggested that SNPs located at UTRs of TLRs pathway genes may potentially influence binding of transcription factors or microRNAs. By applying a pathway-based bioinformatics analysis of genetic variations, we provided a prioritized list of potentially deleterious variants. These findings may facilitate the selection of proper variants for future functional and/or association studies.Show more
    Alipoor B,Ghaedi H,Omrani MD,Bastami M,Meshkani R,Golmohammadi T
    International journal of molecular and cellular medicine
  • The contribution of microRNAs (miRNAs) to cancer has been extensively investigated and it became obvious that a strict regulation of miRNA-mRNA regulatory network is crucial for safeguarding cell Apart from the direct impact of miRNA dysregulation in cancer pathogenesis, genetic variations in miRNAs are likely to disrupt miRNA-target interaction. Indeed, many evidences suggested that SNPs within miRNA regulome are associated with the development of different hematological malignancies. However, a full catalog of SNPs within miRNAs target sites of genes relevant to hematopoiesis and hematological malignancies is still lacking. Accordingly, we aimed to systematically identify and characterize such SNPs and provide a prioritized list of most potentially disrupting SNPs. Although in the present study we did not address the functional significance of these potential disturbing variants, we believe that our compiled results will be valuable for researchers interested in determining the role of target-SNPs in the development of hematological malignancies.Show more
    Ghaedi H,Bastami M,Zare-Abdollahi D,Alipoor B,Movafagh A,Mirfakhraie R,Omrani MD,Masotti A
  • Esophageal, stomach, and colorectal cancers are commonly lethal gastrointestinal tract (GIT) neoplasms, causing almost two million deaths worldwide each year. some environmental risk factors are ackno...wledged; however, genetic defects can significantly contribute to predisposition to GIT cancers. Accordingly, recent works have shown that single-nucleotide polymorphisms (SNPs) within miRNAs coding sequence (miR-SNPs) and miRNA target sites (target-SNPs) may further contribute to increased risk of developing cancer.Show more
    Saadatian Z,Masotti A,Nariman Saleh Fam Z,Alipoor B,Bastami M,Ghaedi H
    Iranian Red Crescent medical journal