Tehran University Medical Journal

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MicroRNAs form a class of small non-coding RNA molecules. With only 21-23 nucleutide in length, they have an important role in gene expression. These molecules bind to their target mRNA molecules and repress the protein expression via mRNA degradation or blocking the translation machine of the cell. From the advent of molecular biology microRNA molecules were out of focus, however huge amount of studies in the past few years revealed a lot of facts about their nature. Nowadays around 1600 different microRNA are discovered in human, animals, plant and even viruses. In this review article the most recent data in the history, genes, expression and process of these molecules are introduced. Furthermore, the findings about diverse roles of these molecules in normal and abnormal conditions, cancer in particular, are shown. Finally, the differences to siRNA molecules and the prospect of microRNA have been explained.

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The prostate is a small gland located below the bladder and upper part of the urethra. In developed countries prostate cancer is the second common cancer (after skin cancer), and also the second leading cause of cancer death (after lung cancer) among men. The several studies have been shown prostate cancer familial aggregation. The main reason for this aggregation is inheritance included genes. The family history is an important risk factor for developing the disease. The genes AR, CYP17, SRD5A2, HSD3B1 and HSD3B2 are all intimately involved in androgen metabolism and cell proliferation in the prostate. Each shows intraspecific polymorphism and variation among racial-ethnic groups that is associated with the risk of prostate cancer. Some of genes expressed in the prostate are in association with the production of seminal fluid and also with prostate cancer. Epigenetic modifications, specifically DNA hypermethylation, are believed to play an important role in the down-regulation of genes important for protection against prostate cancer. In prostate cancer numerous molecular and genetic aberrations have been described. It is now well established that cancer cells exhibit a number of genetic defects in apoptotic pathways. In this review article, the most recent data in molecular genetic, prevention and especially gene therapy in prostate cancer are introduced.

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Background: With approximately 386,000 deaths per year, esophageal cancer is the 6th most common cause of death due to cancer in the world. This cancer, like any other cancer, is the outcome of genetic alterations or environmental factors such as tobacco smoke and gastro-esophageal reflux. Tobacco smoking is a major etiologic factor for esophageal squamous cell carcinoma in western countries, and it increases the risk by approximately 3 to 5 folds. Chronic gastro-esophageal reflux usually leads to the replacement of squamous mucosa by intestinal-type Barrett’s metaplastic mucosa which is considered the most important factor causing esophageal adenocarcinoma. In contrast to esophageal adenocarcinoma, different risk factors and mechanisms, such as mutations in oncogenes and tumor suppressor genes, play an important role in causing esophageal squamous cell carcinoma. Molecular studies on esophageal cancers have revealed frequent genetic abnormalities in esophageal squamous cell carcinoma and adenocarcinoma, including altered expression of p53, p16, cyclin D1, EGFR, E-cadherin, COX-2, iNOS, RARs, Rb, hTERT, p21, APC, c-MYC, VEGF, TGT-α and NF-κB. Many studies have focused on the role of different polymorphisms such as aldehyde dehydrogenase 2 and alcohol dehydrogenase 2 in causing esophageal cancer. Different agents including bestatin, curcumin, black raspberries, 5-lipoxygenase (LOX) and COX-2 inhibitors have been found to play a role in inhibiting esophageal carcinogenesis. Different gene therapy approaches including p53 and p21WAF1 replacement gene therapies and therapy by suicide genes have also been experimented. Moreover, efforts have been made to use nanotechnology and aptamer technology in this regard.

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Cancer is one of the main reasons of mortality worldwide, and more than 90 percent of cancer deaths are due to metastasis. Although primary tumors are curable using chemical adjuvant therapy or surgery, metastatic tumors are mostly incurable. This resistance shows the high rate of mortality among patients with metastatic disease. Being a sequential event, metastasis is a subtle and intricate process in which tumor cells undergo a plenty of changes and acquire the capacity of migration, invasion, survival and self-renewal which all are necessary for metastasis to happen. The key point in recognition and cure in invasive cancers is to identify critical genes, proteins and pathways involved, and show their relation with each other and the disease. Forming metastasis needs favorable genetic and microenvironmental elements of tumor cells and distant tissue, respectively. Unfavorable conditions in each steps of this process lead to arresting metastasis and subsequent dormancy, which is the most important phenomenon in relapse. In this review, benefiting from tens of reliable and recently identified data and personal experiences, it has been tried to draw new patterns associated with metastasis for further investigation. Determining genes, proteins and microenvironmental factors that affect metastasis, in a sequential manner, can help better understanding of this lethal process and subsequently a prosperous treatment.

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Differentiated cells can change to embryonic stem cells by reprograming. Generation of induced pluripotent stem cells (iPSCs) has revolutionized the field of regenerative and personalized medicine. iPSCs can self-renew and differentiate into many cell types. iPSC cells offer a potentially unlimited source for targeted differentiation. Through the expression of a set of transcription factors, iPSCs can be generated from different kinds of embryonic and adult cells. This technology for the first time enabled the researchers to take differentiated cells from an individual, and convert them to another cell type of interest, which is particularly to that person. When the set of master transcription factors containing OCT4, SOX2, KLF4, and MYC is expressed ectopically in somatic cells, the transcriptional network is propelled to organize itself in such a way as to maintenance a pluripotent state. Since iPSCs are similar to Embryonic Stem Cell (ESC), they can be considered as sources for modeling different diseases. iPSCs which are induced from somatic cells of patient can be useful for screening and drugs selection, and also introduce treatment via grafting the cells. Although this technology has been successful in different fields, the tumorigenesis of viral vectors during induction of reprogramming is a major challenge. Nevertheless, iPSCs are valuable for clinical applications and research. By discovery of these cells many challenges related to the safety, efficacy, and bioethics of ESCs are solved. Pluripotency is defined in two aspect of functional and molecular, by which functional regards the capacity of cell is generate three kinds of embryonic layers and germ line, and molecular aspect regards the identifying of molecules and genes that support functional features. Identification of these genes has been placed at the center of fields related to development and stem cell research. In this review, we discuss the process of generation of these cells, as well as required genes and factors for pluripotency, and also current progress in generation of iPSCs utilizing tens of reliable and new studies.

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