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Volume 18, Issue 8 (11-2015)
Background: Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more consecutive pregnancy losses prior to 20th week of gestation. There are several leading causes of RPL including uterine anatomical defects, infections, genetic, immunological, and environmental factors. However, despite in a large number of cases no causes have been identified, therefore, it is introduced as idiopathic.
Recent studies have implicated the role of miRNAs in endometriosis, preeclampsia, infertility and RPL. Therefore, the aim of the present study was to investigate the association of miR-196a2C>T (rs11614913) with RPL in Iranian women.
Materials and Methods: In this case-control study, 183 Iranian women including 83 patients with at least two unexplained consecutive pregnancy losses and 100 healthy controls with at least one live birth and no history of pregnancy loss were investigated. Patients with recurrent pregnancy losses due to anatomic, hormonal, chromosomal, infectious, autoimmune, or thrombotic causes were excluded from the study group. Genotyping was performed using Tetra- ARMS PCR method.
Results: Significant difference in distribution of miR-196a2 rs11614913 genotypes was found in RPL patients in comparison to controls, with p value of 0.04 and odds ratio equal to 2.96 (95% CI: 1.03-7.03).
Conclusion: The results of the present study provide evidence for association between genetic variation in miR-196a2 and recurrent pregnancy loss. Further studies will be required to validate the significance of the studied genetic variation in diverse populations and its regulatory role on target genes.
Volume 19, Issue 5 (8-2016)
Background: Circulating microRNAs are promising biomarkers in diagnosis and assessment of cancerous patients. Quantitative Real-time PCR assay is a sensitive test for evaluating the levels of miRNAs expression. Nevertheless, there is no concurrence on selecting appropriate reference genes for qPCR analysis of miRNAs in circulation. Therefore, the current study aimed to select a suitable reference gene for normalizing the RT-qPCR assay results in plasma samples of patients with gastric cancer.
Materials and Methods: Based on previously published studies, three molecules SNORD47, U6 RNA, and miR-103 were selected as the candidate reference genes. After RNA extraction from plasma samples of 40 patients with gastric cancer and 40 healthy individuals, expression levels of these molecules were evaluated using Real-time PCR method.
Results: The results showed that the developed assays are able to diagnose their specified targets by a suitable linear range. By comparing patients and control groups, although the expression levels of miR-103 molecule were not equal between the two groups (p= 0.017), SNORD47 and U6 RNAs had similar expression levels. However, the variations of SNORD47 expression were lower that U6 RNA.
Conclusion: Based on the results of the current study, the SNORD47 molecule has a stable expression levels in plasma samples of patients with gastric cancer and normal individuals and can be used as an appropriate reference gene for normalizing the quantitative data of qPCR assay.
Volume 19, Issue 12 (3-2017)
Abstract
Background: Hepatocellular carcinoma (HCC) is the third major cause of cancer death worldwide. Hepatitis B virus (HBV) and HBx gene play an important role in the development of HCC by influencing signaling pathways. Since there is no detectable symptom in the early phase of HCC, there is need to find new HCC-specific markers with high sensitivity for early detection and diagnosis of HCC. On the other hand, by the advent and development of bioinformatic sciences, it is now possible to predict miRNAs as biomarkers, and their targets. Therefore, in the present study, based on the results of the bioinformatic software applications with different algorithm, we selected the miRNA targeting HBx and NOTCH1 mRNAs according to higher score, suitable connection with target gene and confirming them in more softwares.
Materials and Methods: First, the sequences of NOTCH1 and HBx genes were retrieved from NCBI. Afterwards, several software applications such as TargetScan, mirWalk, miRBase, Miranda, PicTar, miRVir, and DIANA were applied to predict miRNAs.
Results: Based on the high scoring by bioinformatics softwares and suitable targeting, miR-34a were selected to target NOTCH1 and miR-6510, miR-5193 and miR-214 were chosen to targetHBX gene.
Conclusion: Because of tumor suppression roles of miR-214 and miR-34a, they probably could be used as therapeutic strategy in cancer researches. It is also seems that the miR-5193 could act as a specific marker in Hepatocellular carcinoma.
Volume 20, Issue 9 (12-2017)
Background: DNA-based computing is an emerging research aspect that enables the in-vivo computation and decision making with significant correctness. Recent papers show that the expression level of miRNAs are related to the progress status of some diseases such as cancers and DNA computing is introduced as a low cost and concise technique for detection of these biomarkers. In this paper, DNA-based logic gates are implemented in the laboratory to detect the level of miR-21 as the biomarker of cancer.
Materials and Methods: At the first, required strands for designing DNA gates are synthesized. Then, double stranded gate is generated in laboratory using a temperature gradient that followed by electrophoresis process. This double strand is the computation engine for detecting the miR-21 biomarker. miR-21 is as input in designed gate. At the end, the expression level of miR-21 is identified by measuring the generated fluorescent.
Results: at the first stage, the proposed DNA-based logic gate is evaluated by using the synthesized input strands and then it is experimented on a tumor tissue. Experimental results on synthesized strands show that its detection quality/correctness is 2.5x better than conventional methods.
Conclusion: Experimental results on the tumor tissues are successful and are matched with those are extracted from real time PCR results. Also, the results show that this method is significantly more suitable than real time PCR in view of time and cost.
Volume 21, Issue 6 (12-2018)
| Cancer is a multifactorial Disorder caused by variations in multiple genes coupled with environmental risk factors. The genes involved in the carcinogenesis can be classified into several groups, including proto-oncogenes, tumor suppressor genes, genes involved in genome stability and cell migration. The accumulations of genetic changes lead to tumor mass and formation of new blood vessels to grow. The tumor is not a collection of single cells and has bilateral interactions with its environments. The tumor microenvironment (TME) has a similar function to stem cells niches that affect tumor progression and metastasis. The study of this environment is effective in diagnosis and treatment of cancer and provides valuable and new information for controlling tumor malignancy and risk assessment (1). This paper focuses on TME components and the molecular targets for cancer treatment. Investigating of TME by cellular and molecular profiles indicated that there are different types of cells in this environment that promote neoplastic changes and metastasis and protect the tumor from the immune system and lead to resistance to treatment (2). Among the different types of cells present in the TME, including parenchymal tumor, fibroblasts, epithelial and inflammatory cells, extracellular matrix and signaling molecules, blood and lymph vessels, the highest number of cells are fibroblasts. In the early stages of carcinogenesis, normal fibroblasts prevent tumor growth. The genetic changes of these cells, with the help of inflammatory agents, release the growth factors that directly inhibit tumor-stimulating cells or indirectly inhibit apoptosis by stimulating growth and inducing angiogenesis. Therefore, a complex system of interactions is created by the involvement of a variety of cellular factors and molecular signals (3,4). Within the TME infrastructure, there are interactions of tumor cells with extracellular matrix (ECM), tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), mesenchymal stem cells (MSCs) and endothelial cells (EC). These communications have been established with the help of chemokines, growth factors, matrix metalloprotezes (MMPs) and ECM proteins, that lead to migration, invasion to distant organs and metastasis (5). TME restores tissue and induces metabolic changes in the tumor by making changes in the stromal and immune cells. This remodeling in a TME is similar to around of scar surrounded by different cells (6). Based on tissue type’s cancers, more than 40% of the CAFs can be derived from bone marrow progenitors that are recruited to the growing TME. Although CAFs may also be derived of epithelial cancer cells or stained fibroblasts that differentiate into myofibroblasts. In epithelial tumors, fibroblasts, mainly through the secretion of growth factors and chemokines, led to an altered ECM, and increase signals of proliferation and metastasis, and ultimately lead to tumor progression (7). The ECM also accumulated a scaffold of inflammatory and immune cells, lymph and nerve arteries. In general, in the metastatic phenomenon, the invasive tumors should be able to move, to break up the extracellular matrix of the tissue, to form new blood vessels, to survive in the blood and to stabilize in a new tissue environment. In studies that have been conducted to understand how these capabilities are achieved in cancer cells, TME has been identified as critical to the development of this phenomenon. TME stabilizes invasion of tumor to distant organs via signals to stromal or non-malignant cells and activation of transcription of genes (8,9). Also, angiogenesis precursor cells that are recruited to TME under hypoxic conditions are associated with metastasis. Some studies have shown that miRNA molecules are the main regulator of this activity, leading to changes in fibroblasts in the TME. MiR-21, miR-31, miR-214 and miR-155 play an important role in differentiation of normal fibroblasts to CAF (10). Although miRNAs in TME have not yet been fully identified, some studies indicated that miRNAs produced by TME cells and specially CAFs affect on tumor growth (11). Musumeci and colleagues showed the role of miRNAs in TME in prostate cancer. Their study found that expression of miR-15a and miR-16 down-regulated in fibroblasts of TME in prostate cancer. MiRNAs target oncogenes such as Bcl-2 and WNT pathway components (12). Several strategies have been proposed to remodel TME components in cancer treatment (2). Blocking the recruitment and activation of stromal cells in TME is one of these molecular approaches. Based on this strategy, Avastin has been designed to treat clone and glioblastoma cancer. Some drugs also block the interaction between the TME cells with the tumor and angiogenesis, ECM and inflammatory compounds in TME. Siltuximab is a human anti-IL-6 antibody that inhibits the pathway of IL-6 / STAT3 in cancer cells and its therapeutic effects have been reported in xenografet models. The effect of this drug in the Phase II clinical trials in platinuim-resistant ovarian cancer is under survey. More accurate identification of gene networks and cell pathways will help us improve our understanding of the pathogenesis of cancer and the advancement of therapeutic approaches. Therefore, in addition to controlling the signaling pathway inside the tumor, it is also necessary to identify the TME. Although, despite the recognition of the importance of TME in carcinogenesis, due to the multiplicity of involved cells, the origin of molecular mutations in its components is still not fully detected and requires extensive research in this area. |
Volume 22, Issue 5 (11-2019)
Methods & Materials Afterwards retrieving the sequences of APRIL and BAFF proteins from the NCBI website, by using several programs including miRanda, TargetScan, miRWalk, DIANA and miRDB with different algorithms, the prediction of miRNAs targeting these genes was investigated.
Ethical Considerations This study was approved by the Research Ethics Committee of Arak University of Medical Sciences.
Results Based on the scoring system of bioinformatics programs, “hsa-miR-145-5p” and “hsa-miR-185-5p” were identified as miRNAs targeting APRIL gene, while “hsa-miR-424” and “hsa-miR-497”were miRNAs targeting BAFF gene. They were suggested for the practical studies in future.
Conclusion Based on the important role of APRIL and BAFF genes in the normal process of cell death and B-cell evolution, it seems that the mi-RNAs predicted by bioinformatics programs using different algorithms can be used as a diagnostic molecular biomarker to identify B-cell CLL patients.
Volume 23, Issue 3 (8-2020)
Methods & Materials: First, using the NCBI database, the E6 and E7 gene sequences were obtained for both human papillomavirus types 16 and 18. Then, using the miRBase and RNA22 bioinformatics databases, the most appropriate targeting miRNAs for these genes were selected.
Ethical Considerations: This study was approved by Ethics Committee of Arak University of Medical Sciences.
Results: Based on the P obtained from bioinformatics databases, miRNA including miR-92a-5p (P=7.51e-2), miR-195-3p (P=2.24e-1), miR-34a-5p (P=2.73e-1) and miR-155-5p (P=4.95e-2) were introduced for the two genes E6 and E7.
Conclusion: Results from bioinformatics studies revealed that of the four miRNAs identified, miR-155-5p and miR-92a-5p are probably the targeting miRNAs specific for the E6 and E7 genes, respectively. Therefore, it seems that these miRNAs can be a suitable candidate for in vitro studies in CC patients.
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