Tehran University Medical Journal

Background: The main causes and difficulties of cancer are the imbalance between cell growth and cell death. This event is the results of changes in the expression level of genes related to these mechanisms. Among genes including in this case, death-associated protein kinase (DAPK) can be mentioned. Studies have shown that the expression of genes is influenced by the methylation of promoter regions. The purpose of this research was to evaluate the expression of the mentioned gene and the effect of methylation on the expression of this gene and its relationship with developing breast cancer in women.
Methods: Eighty patients with breast cancer and 80 healthy individuals participated in this case-control study which has been referred to Shahid Faghihi and Namazi hospitals, Shiraz city, from August 2014 to March 2017. This study was carried out at the Genetic Research Center of Islamic Azad University, Kazerun Branch, Iran. Peripheral blood lymphocytes were lysed and the mRNAs were extracted using the InViSorb™ RNA preparation kit II (Cat#1062100300, Invitek GmbH, Berlin, Germany) and cleaned up with Qiagen RNeasy spin columns. The first-strand cDNA was synthesized affording to the high capacity cDNA reverse transcription kit procedure. For DAPK gene expression, (Thermo Fisher Scientific, Waltham, MA, USA) PCR technique combines the quantitative performance of SYBR® Green-based real-time PCR, used. This technique is gainful, easy-to-use, and emphases only on the genes that you want. We designated 18S-rRNA gene, as our house-keeping gene. For determine of methylation, methylation-specific polymerase chain reaction (MS-PCR) method was used. 
Results: The achieved results from this research show that the levels of DAPK gene expression have a significant difference. The rate of expression in patients was significantly reduced compared with the control group (P=0.0156). Also, the relationship between expression of DAPK factor and lymph node involvement was investigated. The results show the relationship between the factors studied. On the other hand, there was no significant relationship between the expression level of this gene and its promoter methylation (P=0.13).
Conclusion: This research shows that reduction in the rate of DAPK gene expression plays an effective role in the patients with breast cancer.

Multiple Sclerosis (MS) is a chronic neurological and inflammatory disorder that affects the nervous system. The etiology of MS is unknown, but genetic and environmental factors are involved in its pathogenesis. There is increasing evidence suggesting the role of epigenetic mechanisms in the pathogenesis of multiple sclerosis. Lack of vitamin D, smoking, and Epstein barr virus can cause epigenetic changes. Several studies have found that Dysregulation in DNA methylation is related to abnormal immune responses and post-translation modifications of myelin proteins in the brain specimens of MS patients. Molecular mechanisms through environmental signals lead to gene expression changes include DNA methylation, post modification of nucleosomal histones and non-coding RNAs. Also, abnormal microRNA profiles have been reported in the brain tissues and peripheral immune blood cells of MS patients. Increased histone acetylation and citrullination of myelin basic protein are two epigenetic mechanisms that may intensify the disease course, in the progressive type. The activation of T cells by histone deacetylase (HDAC) may contribute to the pathogenesis of MS disease and increase the intensity of disease. Increased of HDAC transcripts can also be observed during immune cell activation. Th1 differentiation is produced by HDACs, and the inhibition of these enzymes reduces the production of IFN-γ. The expression of 364 miRNA in peripheral blood mononuclear cell (PBMC) has been reported in the patients with remitting and relapsing and increased miR-18b and miR-599 regulation in the relapsing course. Expression of miRNAs in astrocytes, microglia, and CD8+ T cells also increased. The role of epigenome in this disease can be deduced from epidemiological studies of the geographical location influence, a month of birth, nutritional status (food and vitamin D absorption), and smoking. Despite of the ever-increasing advances, the epigenetic mechanisms of MS are still unknown. Numerous studies are needed to treat and control the disease and discover new and effective drugs due to the complexity of multiple sclerosis and the importance of epigenetic changes in multiple signaling pathways and the molecular mechanisms of different types of MS.

Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), hepatitis B virus (HBV), human papilloma virus (HPV), Merkel cell polyomavirus (MCPyV), human lymphotropic virus type 1 (HTLV-1) and Hepatitis C virus (HCV) are among the most important viruses that cause cancer in humans. These viruses are collectively known as oncoviruses due to their potential to induce malignant transformations in host cells. Oncoviruses exert their cancer-causing effects by utilizing various viral oncoproteins and non-coding RNAs, which can drive host cells toward malignancy through multiple pathways. One critical strategy these viruses employ involves altering the host cell's regulatory mechanisms, particularly by influencing DNA methylation processes.
DNA methylation is a crucial modification that occurs on the promoter regions of genes, effectively reducing their expression levels. Under normal cellular conditions, a delicate balance of methylation and demethylation is maintained by a specific set of enzymes. Key players in this process include DNA methyltransferases (DNMTs) and TET methylcytosine dioxygenases (TETs), which are pivotal in regulating gene expression through methylation. These enzymes are prime targets for oncoviruses because, by altering their activity, viruses can hijack the host cell's regulatory machinery. Viral oncoproteins, though diverse in structure and function, often converge on disrupting the expression of these enzymes. By doing so, they induce widespread changes in DNA methylation patterns, effectively reprogramming the gene expression landscape of the host cell. This reprogramming is not random; rather, it is a calculated mechanism through which oncoviruses can manipulate the cell cycle, promoting uncontrolled cellular proliferation and progression towards cancer. By suppressing or activating specific genes, these viruses can push cells past normal checkpoints, eventually leading to tumor formation. Despite the critical role of DNA methylation in cancer development, the precise mechanisms by which oncoviruses modulate these methylation processes are not fully understood. Researchers have made significant progress in exploring the connection between viral infections and cancer, but many of the detailed pathways through which oncoviruses control methylation remain to be elucidated. As a result, this area remains a fertile ground for further research, offering potential avenues for therapeutic intervention in virus-induced cancers.