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Tao Su, Xia Yang, Jian-Hua Deng, Qiu-Ju Huang, Su-Chao Huang, Yan-Min Zhang, Hong-Ming Zheng, Ying Wang, Lin-Lin Lu, Zhong-Qiu Liu
Lung cancer is a leading cause of cancer-related deaths worldwide. NOTCH3 signaling is mainly expressed in non-small cell lung carcinoma (NSCLC), and has been proposed as a therapeutic target of NSCLC. While, few agents for preventing or treating NSCLC via targeting NOTCH3 signaling are used in modern clinical practice. Evodiamine (EVO), an alkaloid derived from Euodiae Fructus, possesses low toxicity and has long been shown to exert anti-lung cancer activity. However, the underlying anti-lung cancer mechanisms of EVO are not yet fully understood...
2018: Frontiers in Pharmacology
Shohei Utsumi, Kousuke Sato, Satoshi Ichikawa
DNA cytosine-5 methyltransferase (DNMT) catalyzes methylation at the C5 position of cytosine in the CpG sequence in double stranded DNA to give 5-methylCpG (mCpG) in the epigenetic regulation step in human cells. The entire reaction mechanism of DNMT is divided into six steps, which are scanning, recognition, flipping, loop locking, methylation, and releasing. The methylation and releasing mechanism are well-investigated; however, few reports are known about other reaction steps. To obtain insight into the reaction mechanism, we planned the incorporation of acyclic nucleosides, which make it easy to flip out the target nucleobase, into oligodeoxynucleotides (ODNs) and investigated the interaction between the ODN and DNMT...
May 5, 2018: Bioorganic & Medicinal Chemistry Letters
Yifan Yang, Zhu Jin, Rui Dong, Chao Zheng, Yanlei Huang, Yijie Zheng, Zhen Shen, Gong Chen, Xiaoying Luo, Shan Zheng
Biliary atresia is one of the most common liver disease in infancy. The cause and pathogenesis remain largely unknown. This study aimed to investigate the potential regulatory effect of miR-29b/142-5p on IFN-γ gene methylation. miRNAs microarray was performed on four pairs of liver and blood specimens from biliary atresia and choledochal cysts. We found the overexpression of miR-142-5p and mRNA level of DNA methyltransferase (DNMT) 1, and miR-29b and DNMT3a/DNMT3b were significantly negatively correlated in biliary atresia livers...
May 10, 2018: Cell Death & Disease
Di Cui, Xiangru Xu
Ageing, a leading cause of the decline/deficits in human learning, memory, and cognitive abilities, is a major risk factor for age-associated neurodegenerative disorders such as Alzheimer’s disease. Emerging evidence suggests that epigenetics, an inheritable but reversible biochemical process, plays a crucial role in the pathogenesis of age-related neurological disorders. DNA methylation, the best-known epigenetic mark, has attracted most attention in this regard. DNA methyltransferases (DNMTs) are key enzymes in mediating the DNA methylation process, by which a methyl group is transferred, faithfully or anew, to genomic DNA sequences...
April 28, 2018: International Journal of Molecular Sciences
Jia Yu, Bo Qin, Ann M Moyer, Somaira Nowsheen, Tongzheng Liu, Sisi Qin, Yongxian Zhuang, Duan Liu, Shijia W Lu, Krishna R Kalari, Daniel W Visscher, John A Copland, Sarah A McLaughlin, Alvaro Moreno-Aspitia, Donald W Northfelt, Richard J Gray, Zhenkun Lou, Vera J Suman, Richard Weinshilboum, Judy C Boughey, Matthew P Goetz, Liewei Wang
Triple-negative breast cancer (TNBC) is a heterogeneous disease with poor prognosis that lacks targeted therapies, especially in patients with chemotherapy-resistant disease. Since DNA methylation-induced silencing of tumor suppressors is common in cancer, reversal of promoter DNA hypermethylation by 5-aza-2'-deoxycytidine (decitabine), an FDA-approved DNA methyltransferase (DNMT) inhibitor, has proven effective in treating hematological neoplasms. However, its antitumor effect varies in solid tumors, stressing the importance of identifying biomarkers predictive of therapeutic response...
April 30, 2018: Journal of Clinical Investigation
Saghar Saeedabadi, Amir Hossein Abazari-Kia, Hoda Rajabi, Kazem Parivar, Mohammad Salehi
Background: DNA methylation is one the epigenetic mechanisms, which is critically involved in gene expression. This phenomenon is mediated by DNA methyl-transferases and is affected by environmental stress, including in vitro maturation (IVM) of oocytes. Melatonin, as an antioxidant, may theoretically be involved in epigenetic regulation via reductions of reactive oxygen species. This study was performed to investigate DNA methylation and the possibility of goat oocyte development after treatment with different concentrations of melatonin...
July 2018: International Journal of Fertility & Sterility
Agnieszka Wnuk, Joanna Rzemieniec, Ewa Litwa, Władysław Lasoń, Małgorzata Kajta
Current evidence indicates that benzophenone-3 (BP-3) can pass through the placental and blood-brain barriers and thus can likely affect infant neurodevelopment. Despite widespread exposure, data showing the effects of BP-3 on the developing nervous system are scarce. This study revealed for the first time that prenatal exposure to BP-3 led to apoptosis and neurotoxicity, altered the levels of estrogen receptors (ERs) and changed the epigenetic status of mouse neurons. In the present study, multiple subcutaneous injections of pregnant mice with BP-3 at 50 mg/kg, which is an environmentally relevant dose, evoked activation of caspase-3 and lactate dehydrogenase (LDH) release as well as substantial loss of mitochondrial membrane potential in neocortical cells of their embryonic offspring...
April 25, 2018: Journal of Steroid Biochemistry and Molecular Biology
Saurabh Pandey, Hem Chandra Jha, Sanket Kumar Shukla, Meghan K Shirley, Erle S Robertson
Helicobacter pylori and Epstein-Barr virus (EBV) are two well-known contributors to cancer and can establish lifelong persistent infection in the host. This leads to chronic inflammation, which also contributes to development of cancer. Association with H. pylori increases the risk of gastric carcinoma, and coexistence with EBV enhances proliferation of infected cells. Further, H. pylori -EBV coinfection causes chronic inflammation in pediatric patients. We have established an H. pylori -EBV coinfection model system using human gastric epithelial cells...
April 24, 2018: MBio
Manish Mishra, Renu A Kowluru
In the development of diabetic retinopathy, retinal mitochondria are dysfunctional, and mitochondrial DNA (mtDNA) is damaged with increased base mismatches and hypermethylated cytosines. DNA methylation is also a potential source of mutation, and in diabetes, the noncoding region, the displacement loop (D-loop), experiences more methylation and base mismatches than other regions of the mtDNA. Our aim was to investigate a possible crosstalk between mtDNA methylation and base mismatches in the development of diabetic retinopathy...
April 21, 2018: Molecular Neurobiology
Paulina Natalia Kopa, Rafał Pawliczak
Cigarette smoke has an crucial impact on transcriptome alteration by its effect on chromatin remodeling and DNA methylation status. The first mechanism is associated with the histone acetylation/deacetylation balance damage as a result of increased activity of NFĸB and lipid peroxidation products, which lead to an increased activity of HATs and DNMTs and reduced HDACs. The second mechanism is connected with direct damaging of DNA by smoke components, activation of downstream repair mechanism and recruitment of DNMTs into the breakage site, "nicotine effect" and carbon monoxide activity on gene transcription and DNA methylation reduction...
April 16, 2018: Toxicology Mechanisms and Methods
Tong Jin, Jianyu Hao, Daiming Fan
Tobacco smoking is an independent risk factor for the initiation of pancreatic cancer (PC). Hypermethylation of tumor suppressor genes has been demonstrated to be associated with smoking. This study aimed to find the relationship between nicotine exposure and hypermethylation of tumor suppressor genes in normal pancreatic epithelial cells. Human pancreatic epithelial cells ware cultured exposing to nicotine and the methylation status of tumor suppressor genes were detected. Proenkephalin (PENK) was chosen as the target gene and methylation level of PENK promoter region was measured...
April 4, 2018: Biochemical and Biophysical Research Communications
M Samiec, M Skrzyszowska
The efficiency of somatic cell cloning in mammals remains disappointingly low. Incomplete and aberrant reprogramming of epigenetic memory of somatic cell nuclei in preimplantation nuclear- transferred (NT) embryos is one of the most important factors that limit the cloning effectiveness. The extent of epigenetic genome-wide alterations, involving histone or DNA methylation and histone deacetylation, that are mediated by histone-lysine methyltransferases (HMTs) or DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) can be modulated/reversed via exogenous inhibitors of these enzymes throughout in vitro culture of nuclear donor cells, nuclear recipient oocytes and/or cloned embryos...
March 2018: Polish Journal of Veterinary Sciences
David Alvarez-Ponce, María Torres-Sánchez, Felix Feyertag, Asmita Kulkarni, Taylen Nappi
DNA methylation is mediated by a conserved family of DNA methyltransferases (Dnmts). The human genome encodes three active Dnmts (Dnmt1, Dnmt3a and Dnmt3b), the tRNA methyltransferase Dnmt2, and the regulatory protein Dnmt3L. Despite their high degree of conservation among different species, genes encoding Dnmts have been duplicated and/or lost in multiple lineages throughout evolution, indicating that the DNA methylation machinery has some potential to undergo evolutionary change. However, little is known about the extent to which this machinery, or the methylome, varies among vertebrates...
2018: PloS One
Massimiliano Manzo, Christina Ambrosi, Tuncay Baubec
Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) is currently the method of choice to determine binding sites of chromatin-associated factors in a genome-wide manner. Here, we describe a method to investigate the binding preferences of mammalian DNA methyltransferases (DNMT) based on ChIP-seq using biotin-tagging. Stringent ChIP of DNMT proteins based on the strong interaction between biotin and avidin circumvents limitations arising from low antibody specificity and ensures reproducible enrichment...
2018: Methods in Molecular Biology
Antonia M Savarese, Amy W Lasek
Alcohol use disorder (AUD) is a chronic relapsing brain disease that currently afflicts over 15 million adults in the United States. Despite its prevalence, there are only three FDA-approved medications for AUD treatment, all of which show limited efficacy. Because of their ability to alter expression of a large number of genes, often with great cell-type and brain-region specificity, transcription factors and epigenetic modifiers serve as promising new targets for the development of AUD treatments aimed at the neural circuitry that underlies chronic alcohol abuse...
March 29, 2018: Handbook of Experimental Pharmacology
Chenhuan Xu, Victor G Corces
The faithful inheritance of the epigenome is critical for cells to maintain gene expression programs and cellular identity across cell divisions. We mapped strand-specific DNA methylation after replication forks and show maintenance of the vast majority of the DNA methylome within 20 minutes of replication and inheritance of some hemimethylated CpG dinucleotides (hemiCpGs). Mapping the nascent DNA methylome targeted by each of the three DNA methyltransferases (DNMTs) reveals interactions between DNMTs and substrate daughter cytosines en route to maintenance methylation or hemimethylation...
March 9, 2018: Science
Annabelle Congras, Nina Caillet, Nouritza Torossian, Cathy Quelen, Camille Daugrois, Pierre Brousset, Laurence Lamant, Fabienne Meggetto, Coralie Hoareau-Aveilla
Systemic anaplastic large-cell lymphoma (ALCL) is a childhood T cell neoplasm defined by the presence or absence of translocations that lead to the ectopic expression of anaplastic lymphoma kinase (ALK), with nucleophosmin-ALK (NPM-ALK) fusions being the most common. Polychemotherapy involving doxorubicin is the standard first-line treatment but for the 25 to 35% of patients who relapse and develop resistance the prognosis remains poor. We studied the potential role of the microRNA miR-125b in the development of resistance to doxorubicin in NPM-ALK(+) ALCL...
March 6, 2018: Oncotarget
Akash K George, Jyotirmaya Behera, Kimberly E Kelly, Nandan K Mondal, Kennedy P Richardson, Neetu Tyagi
Chronic ethanol/alcohol (AL) dosing causes an elevation in homocysteine (Hcy) levels, which leads to the condition known as Hyperhomocysteinemia (HHcy). HHcy enhances oxidative stress and blood-brain-barrier (BBB) disruption through modulation of endoplasmic reticulum (ER) stress; in part by epigenetic alternation, leading to cognitive impairment. Clinicians have recommended exercise as a therapy; however, its protective effect on cognitive functions has not been fully explored. The present study was designed to observe the protective effects of exercise (EX) against alcohol-induced epigenetic and molecular alterations leading to cerebrovascular dysfunction...
March 26, 2018: Scientific Reports
C Yang, J Ye, Y Liu, J Ding, H Liu, X Gao, X Li, Y Zhang, J Zhou, X Zhang, W Huang, F Fang, Y Ling
Puberty is initiated by increased pulsatile gonadotropin-releasing hormone (GnRH) release from the hypothalamus. Epigenetic repression is thought to play a crucial role in the initiation of puberty, although the existence of analogous changes in methylation patterns across species is unclear. We analysed mRNA expression of DNA methyltransferases (DNMTs) and methyl-binding proteins (MBPs) in goats and rats by quantitative real-time PCR (qRT-PCR). DNA methylation profiles of hypothalamic were determined at the pre-pubertal and pubertal stages by bisulphite sequencing...
March 25, 2018: Reproduction in Domestic Animals, Zuchthygiene
Rosa Jahangiri, Fatemeh Mosaffa, Amirnader Emami Razavi, Ladan Teimoori-Toolabi, Khadijeh Jamialahmadi
Tamoxifen is a standard anti-hormone treatment in estrogen receptor positive breast carcinoma patients. Unfortunately, about 50% of patients relapse during treatment. Promoter hypermethylation contributes to the epigenetic modulation of tamoxifen resistance-related genes. To evaluate the contribution of DNMTs expression and their promoter methylation as diagnostic biomarkers in development of breast malignancy and tamoxifen resistance, the present study was designed and 107 breast tumors and normal breast tissues were recruited...
March 25, 2018: Journal of Cellular Physiology
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