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https://www.readbyqxmd.com/read/28926119/procaine-is-a-specific-dna-methylation-inhibitor-with-anti-tumor-effect-for-human-gastric-cancer
#1
Yong-Chao Li, Yun Wang, Dan-Dan Li, Ying Zhang, Tian-Cheng Zhao, Chang-Feng Li
DNA hypermethylation and the silencing of tumor suppressor genes caused by DNA hypermethylation is considered as a molecular hallmark of many kinds of cancers. Procaine, a local anesthetic, has been shown as a potential DNA methylation inhibitor in some types of cancers. However, the influence of procaine on DNA methylation regulation as well as the biological function in gastric cancer is still unknown. We report here that procaine represses the DNA-methylation level and promotes the proliferation arrest and apoptosis of gastric cancer cells...
September 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28925878/genistein-induces-alterations-of-epigenetic-modulatory-signatures-in-human-cervical-cancer-cells
#2
Madhumitha Kedhari Sundaram, Mohammad Zeeshan Ansari, Abdullah Al Mutery, Maryam Ashraf, Reem Nasab, Sheethal Rai, Naushad Rais, Arif Hussain
Introduction Epidemiological studies indicate that diet rich in fruits and vegetables are associated with decreased cancer risk thereby indicating that dietary polyphenols can be potential chemo-preventive agents. The reversible nature of epigenetic modifications makes them a favorable target for cancer prevention. Polyphenols have been shown to reverse aberrant epigenetic patterns by targeting the regulatory enzymes, DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). In vitro and in silico studies of DNMTs and HDACs were planned to examine genistein's role as a natural epigenetic modifier in human cervical cancer cells, HeLa...
September 18, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28900200/differential-landscape-of-non-cpg-methylation-in-embryonic-stem-cells-and-neurons-caused-by-dnmt3s
#3
Jong-Hun Lee, Sung-Joon Park, Kenta Nakai
Methylated non-CpGs (mCpH; H means A, C, and T) have emerged as key epigenetic marks in mammalian embryonic stem cells (ESCs) and neurons, regulating cell type-specific functions. In these two cell types, mCpHs show distinct motifs and correlations to transcription that could be a key in understanding the cell type-specific regulations. Thus, we attempted to uncover the underlying mechanism of the differences in ESCs and neurons by conducting a comprehensive analysis of public whole genome bisulfite sequencing data...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28893564/5-aza-2-deoxycytidine-induces-human-tenon-s-capsule-fibroblasts-differentiation-and-fibrosis-by-up-regulating-tgf-%C3%AE-type-i-receptor
#4
Shuhao Fu, Li Sun, Xiaoyan Zhang, Huimin Shi, Kang Xu, Yiqin Xiao, Wen Ye
The principle reason of high failure rate of glaucoma filtration surgery is the loss of filtration function caused by postoperative scar formation. We investigated the effects of 5-aza-2'-deoxycytidine (5-Aza-dc), a DNA methyltransferases inhibitor, on human Tenon's capsule fibroblasts (HTFs) differentiation and fibrosis and its mechanism of action, especially in relation to transforming growth factor (TGF)-β1 signaling. TGF-β1 was used to induce differentiation of cultured HTFs. 5-Aza-dc suppressed DNA methyltransferases (DNMTs) activity 6 h after treatment with a course corresponding to that of TGF-β1-induced reduction of DNMT activity without affecting cell viability as measured by Cell Counting Kit-8 assay...
September 9, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28886082/haloperidol-induces-pharmacoepigenetic-response-by-modulating-mirna-expression-global-dna-methylation-and-expression-profiles-of-methylation-maintenance-genes-and-genes-involved-in-neurotransmission-in-neuronal-cells
#5
Babu Swathy, Moinak Banerjee
INTRODUCTION: Haloperidol has been extensively used in various psychiatric conditions. It has also been reported to induce severe side effects. We aimed to evaluate whether haloperidol can influence host methylome, and if so what are the possible mechanisms for it in neuronal cells. Impact on host methylome and miRNAs can have wide spread alterations in gene expression, which might possibly help in understanding how haloperidol may impact treatment response or induce side effects. METHODS: SK-N-SH, a neuroblasoma cell line was treated with haloperidol at 10μm concentration for 24 hours and global DNA methylation was evaluated...
2017: PloS One
https://www.readbyqxmd.com/read/28864009/negative-uterine-asynchrony-retards-early-equine-conceptus-development-and-upregulation-of-placental-imprinted-genes
#6
Charlotte Gibson, Marta de Ruijter-Villani, Tom A E Stout
INTRODUCTION: Placental imprinted genes appear to be sensitive indicators of an inappropriate pre-implantation environment. This study examined the effects of negative uterine asynchrony after embryo transfer (ET) on early horse embryo development, and yolk-sac membrane expression of DNA methyltransferases (DNMTs) and equine specific placental imprinted genes. METHODS: Day 8 embryos were transferred to recipient mares on day 8 (synchronous) or day 3 (asynchronous) after ovulation, and conceptuses were recovered 6 or 11 days later (day 14 or 19 of development)...
September 2017: Placenta
https://www.readbyqxmd.com/read/28859886/atrazine-exposure-decreases-the-activity-of-dnmts-global-dna-methylation-levels-and-dnmt-expression
#7
Sara E Wirbisky-Hershberger, Oscar F Sanchez, Katharine A Horzmann, Devang Thanki, Chongli Yuan, Jennifer L Freeman
Atrazine, a herbicide used on agricultural crops is widely applied in the Midwestern United States as well as other areas of the globe. Atrazine frequently contaminates potable water supplies and is a suspected endocrine disrupting chemical. Previous studies have reported morphological, hormonal, and molecular alterations due to developmental and adulthood atrazine exposure; however, studies examining epigenetic alterations are limited. In this study, the effects of atrazine exposure on DNA methyltransferase (DNMT) activity and kinetics were evaluated...
August 30, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28842590/ddx3-localizes-to-the-centrosome-and-prevents-multipolar-mitosis-by-epigenetically-and-translationally-modulating-p53-expression
#8
Wei-Ju Chen, Wei-Ting Wang, Tsung-Yuan Tsai, Hao-Kang Li, Yan-Hwa Wu Lee
The DEAD-box RNA helicase DDX3 plays divergent roles in tumorigenesis, however, its function in mitosis is unclear. Immunofluorescence indicated that DDX3 localized to centrosome throughout the cell cycle and colocalized with centrosome-associated p53 during mitosis in HCT116 and U2OS cells. DDX3 depletion promoted chromosome misalignment, segregation defects and multipolar mitosis, eventually leading to G2/M delay and cell death. DDX3 prevented multipolar mitosis by inactivation and coalescence of supernumerary centrosomes...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801263/glucocorticoids-regulate-mir-29c-levels-in-vascular-smooth-muscle-cells-through-transcriptional-and-epigenetic-mechanisms
#9
Tsai-Der Chuang, Omid Khorram
AIMS: The objective of this study was to determine the underlying mechanism by which glucocorticoids (GCs) induce of miR-29c expression in vascular smooth muscle cells. MAIN METHODS: QRT-PCR was used for miR-29c detection. Protein levels were determined by western blotting. Knockdown of SP1, DNMT1 and DNMT3A was achieved through transfection with their specific respective siRNAs. The effect of GCs on SP1 activity was determined by luciferase reporter assay and the methylation status in miR-29c promoter was detected by methylation specific PCR...
October 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28795598/inhibition-studies-of-dna-methyltransferases-by-maleimide-derivatives-of-rg108-as-non-nucleoside-inhibitors
#10
Grégoire Rondelet, Laurence Fleury, Céline Faux, Véronique Masson, Jean Dubois, Paola B Arimondo, Luc Willems, Johan Wouters
AIM: DNA methyltransferases (DNMTs) are important drug targets for epigenetic therapy of cancer. Nowadays, non-nucleoside DNMT inhibitors are in development to address high toxicity of nucleoside analogs. However, these compounds still have low activity in cancer cells and mode of action of these compounds remains unclear. MATERIALS & METHODS: In this work, we studied maleimide derivatives of RG108 by biochemical, structural and computational approaches to highlight their inhibition mechanism on DNMTs...
August 10, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28780164/changes-in-epigenetic-markers-dnmt1-and-hdac1-2-in-the-adult-mouse-hippocampus-after-cranial-irradiation
#11
Sohi Kang, Yeonghoon Son, Sueun Lee, Juhwan Kim, Jong-Choon Kim, Joong-Sun Kim, Uhee Jung, Sung-Ho Kim, Miyoung Yang, Changjong Moon
Brain exposure to ionizing radiation can cause functional deficits in the hippocampus, including memory impairment. However, the specific molecular mechanisms underlying irradiation-induced cognitive impairments are largely unknown. Changes in DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), which are involved in DNA methylation and histone remodeling, may be associated with behavioral changes in learning and memory. We assessed changes in the levels of enzymes associated with the epigenetic modification of gene expression, including DNMT1, HDAC1, HDAC2, Sirtuin 1 (SIRT1), and acetylated histone H3 (Ace-H3) in the mouse hippocampus 1 and 30days after a single exposure to cranial irradiation (0 or 10Gy)...
September 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28764788/regulation-of-human-glioma-cell-apoptosis-and-invasion-by-mir-152-3p-through-targeting-dnmt1-and-regulating-nf2-mir-152-3p-regulate-glioma-cell-apoptosis-and-invasion
#12
Jin Sun, Xinhua Tian, Junqing Zhang, Yanlin Huang, Xiaoning Lin, Luyue Chen, Shizhong Zhang
BACKGROUND: MiRNAs are involved in aberrant DNA methylation through regulation of DNA methyltransferases (DNMTs) in the pathogenesis and progression of glioblastomas (GBM). MiR-152-3p was down-expressed in human malignancies, and served as a tumor suppressor. Neurofibromatosis type 2 (NF2) was significantly decreased in GBM tissues with a high level of methylation. However, the link between miR-152-3p, DNMT1 and methylation of NF2 in GBM is not clearly established. This study was conducted to detect the mechanism between miR-152-3p, DNMT1 and NF2 in GBM...
August 1, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28752221/dna-methylation-profiles-in-cancer-diagnosis-and-therapeutics
#13
REVIEW
Yunbao Pan, Guohong Liu, Fuling Zhou, Bojin Su, Yirong Li
Cancer initiation and proliferation is regulated by both epigenetic and genetic events with epigenetic modifications being increasingly identified as important targets for cancer research. DNA methylation catalyzed by DNA methyltransferases (DNMTs) is one of the essential epigenetic mechanisms that control cell proliferation, apoptosis, differentiation, cell cycle, and transformation in eukaryotes. Recent progress in epigenetics revealed a deeper understanding of the mechanisms of tumorigenesis and provided biomarkers for early detection, diagnosis, and prognosis in cancer patients...
July 27, 2017: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/28750405/untargeted-dna-demethylation-therapy-neither-prevents-nor-attenuates-ischemia-reperfusion-induced-renal-fibrosis
#14
Benjamin A Vervaet, Lies Moonen, Lode Godderis, Katrien Poels, Patrick C D'Haese
BACKGROUND: Current treatment options for chronic kidney disease (CKD) are limited and their focus is on slowing its progression by addressing comorbidities. Fibrosis, the common histopathological process in CKD, is a major therapeutic research target. In CKD, fibroblasts are terminally activated due to alterations in their DNA-methylation pattern, particularly hypermethylation. Preventing the copying of pathological DNA-methylation patterns in proliferating fibroblasts could be a new effective therapeutic strategy for treating CKD...
July 28, 2017: Nephron
https://www.readbyqxmd.com/read/28749461/dnmt1-maintained-hypermethylation-of-kr%C3%A3-ppel-like-factor-5-involves-in-the-progression-of-clear-cell-renal-cell-carcinoma
#15
Rong-Jie Fu, Wei He, Xiao-Bo Wang, Lei Li, Huan-Bin Zhao, Xiao-Ye Liu, Zhi Pang, Guo-Qiang Chen, Lei Huang, Ke-Wen Zhao
Clear cell renal cell carcinoma (ccRCC) is the major subtype of renal cell carcinoma (RCC) that is resistant to conventional radiation and chemotherapy. It is a challenge to explore effective therapeutic targets and drugs for this kind of cancer. Transcription factor Krüppel-like factor 5 (KLF5) exerts diverse functions in various tumor types. By analyzing cohorts of the Cancer Genome Atlas (TCGA) data sets, we find that KLF5 expression is suppressed in ccRCC patients and higher level of KLF5 expression is associated with better prognostic outcome...
July 27, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28740121/overexpression-of-dnmt3b-target-genes-during-enteric-nervous-system-development-contribute-to-the-onset-of-hirschsprung-disease
#16
Leticia Villalba-Benito, Ana Torroglosa, Raquel María Fernández, Macarena Ruíz-Ferrer, María José Moya-Jiménez, Guillermo Antiñolo, Salud Borrego
Hirschsprung disease (HSCR) is attributed to a failure of neural crest cells (NCCs) to migrate, proliferate, differentiate and/or survive in the bowel wall during embryonic Enteric Nervous System (ENS) development. ENS formation is the result from a specific gene expression pattern regulated by epigenetic events, such DNA methylation by the DNA methyltransferases (DNMTs), among other mechanisms. Specifically, DNMT3b de novo methyltransferase is associated with NCCs development and has been shown to be implicated in ENS formation and in HSCR...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28732309/zebularine-induces-replication-dependent-double-strand-breaks-which-are-preferentially-repaired-by-homologous-recombination
#17
Manuel Luis Orta, Nuria Pastor, Estefanía Burgos-Morón, Inmaculada Domínguez, José Manuel Calderón-Montaño, Carlos Huertas Castaño, Miguel López-Lázaro, Thomas Helleday, Santiago Mateos
Zebularine is a second-generation, highly stable hydrophilic inhibitor of DNA methylation with oral bioavailability that preferentially target cancer cells. It acts primarily as a trap for DNA methyl transferases (DNMTs) protein by forming covalent complexes between DNMT protein and zebularine-substrate DNA. It's well documented that replication-blocking DNA lesions can cause replication fork collapse and thereby to the formation of DNA double-strand breaks (DSB). DSB are dangerous lesions that can lead to potentially oncogenic genomic rearrangements or cell death...
July 12, 2017: DNA Repair
https://www.readbyqxmd.com/read/28720666/inactivation-of-receptor-tyrosine-kinases-reverts-aberrant-dna-methylation-in-acute-myeloid-leukemia
#18
Na Shen, Fei Yan, Jiuxia Pang, Na Zhao, Naseema Gangat, Lai-Chu Wu, Ann M Bode, Aref Al-Kali, Mark R Litzow, Shujun Liu
Purpose: Receptor tyrosine kinases (RTKs) are frequently deregulated in leukemia, yet the biological consequences of this deregulation remain elusive. The mechanisms underlying aberrant methylation, a hallmark of leukemia, are not fully understood. Here we investigated the role of RTKs in methylation abnormalities and characterized the hypomethylating activities of RTK inhibitors.<br />Experimental Design: Whether and how RTKs regulate expression of DNA methyltransferases (DNMTs), tumor suppressor genes (TSGs) as well as global and gene specific DNA methylation were examined...
July 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28716037/phylogeny-expression-patterns-and-regulation-of-dna-methyltransferases-in-early-development-of-the-flatfish-solea-senegalensis
#19
Joana Firmino, Carlos Carballo, Paula Armesto, Marco A Campinho, Deborah M Power, Manuel Manchado
BACKGROUND: The identification of DNA methyltransferases (Dnmt) expression patterns during development and their regulation is important to understand the epigenetic mechanisms that modulate larval plasticity in marine fish. In this study, dnmt1 and dnmt3 paralogs were identified in the flatfish Solea senegalensis and expression patterns in early developmental stages and juveniles were determined. Additionally, the regulation of Dnmt transcription by a specific inhibitor (5-aza-2'-deoxycytidine) and temperature was evaluated...
July 17, 2017: BMC Developmental Biology
https://www.readbyqxmd.com/read/28712054/alcohol-exposure-promotes-dna-methyltransferase-dnmt3a-upregulation-through-reactive-oxygen-species-dependent-mechanisms
#20
Federico Miozzo, Hélène Arnould, Aurélie de Thonel, Anne-Laure Schang, Délara Sabéran-Djoneidi, Anne Baudry, Benoît Schneider, Valérie Mezger
Abundant evidence has accumulated showing that fetal alcohol exposure broadly modifies DNA methylation profiles in the brain. DNA methyltransferases (DNMTs), the enzymes responsible for DNA methylation, are likely implicated in this process. However, their regulation by ethanol exposure has been poorly addressed. Here, we show that alcohol exposure modulates DNMT protein levels through multiple mechanisms. Using a neural precursor cell line and primary mouse embryonic fibroblasts (MEFs), we found that ethanol exposure augments the levels of Dnmt3a, Dnmt3b, and Dnmt3l transcripts...
July 15, 2017: Cell Stress & Chaperones
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