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https://www.readbyqxmd.com/read/28430656/thyroid-cancer-1-c8orf4-shows-high-expression-no-mutation-and-reduced-methylation-level-in-lung-cancers-and-its-expression-correlates-with-%C3%AE-catenin-and-dnmt1-expression-and-poor-prognosis
#1
Yi-Wen Zheng, Li Zhang, Yuan Wang, Song-Yan Chen, Lei Lei, Na Tang, Da-Lei Yang, Lin-Lin Bai, Xiu-Peng Zhang, Gui-Yang Jiang, Lian-He Yang, Hong-Tao Xu, Qing-Chang Li, Xue-Shan Qiu, En-Hua Wang
Thyroid cancer 1 (TC1, C8orf4) plays important roles in tumors. The aim of this study was to examine the protein expression levels, methylation status, and mutational status of TC1 (C8orf4) in lung cancers, and investigate the correlation between TC1, other members of the Wnt signaling pathway, and lung cancer. TC1 expression levels were assessed via immunohistochemical staining in 179 cases of lung cancer. β-catenin, TCF4, Axin, Disabled-2, Chibby, and DNA methyltransferase-1 (DNMT1) expressions were also examined...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429280/synergistic-anti-cancer-effects-of-epigenetic-drugs-on-medulloblastoma-cells
#2
Juan Yuan, Núria Llamas Luceño, Bjoern Sander, Monika M Golas
PURPOSE: Medulloblastomas are aggressive brain malignancies. While considerable progress has been made in the treatment of medulloblastoma patients with respect to overall survival, these patients are still at risk of developing neurologic and cognitive deficits as a result of anti-cancer therapies. It is hypothesized that targeted molecular therapies represent a better treatment option for medulloblastoma patients. Therefore, the aim of the present study was to test a panel of epigenetic drugs for their effect on medulloblastoma cells under mild hypoxic conditions that reflect the physiological concentrations of oxygen in the brain...
April 20, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28427182/identification-of-dbccr1-as-a-suppressor-in-the-development-of-lung-cancer-that-is-associated-with-increased-dna-methyltransferase-1
#3
Guoren Zhou, Jinjun Ye, Ying Fang, Zhi Zhang, Jingyuan Zhang, Lei Sun, Jifeng Feng
Accumulating evidence has pointed to a role of the CpG island hypermethylation in the regulation of cancer-related genes in tumor progression. However, the biological impacts in cancer pathogenesis associated with down-regulation of such gene targets remains elusive. Here we focused on a potential target of hypermethylation, DBCCR1 (deleted in bladder cancer chromosome region 1), a gene encoding a candidate tumor suppressor. We found that the expression of DBCCR1 is significantly lower in the lung cancer tissues compared with adjacent non-tumor tissues of patients...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28425161/atorvastatin-treatment-modulates-p16-promoter-methylation-to-regulate-p16-expression
#4
Boqian Zhu, Yaoyao Gong, Gaoliang Yan, Dong Wang, Qingjie Wang, Yong Qiao, Jiantong Hou, Bo Liu, Chengchun Tang
Intimal hyperplasia, the key event of artery restenosis, was a result of cell proliferation and cell migration. Atorvastatin experts an inhibitory effect on cell proliferation and migration but its mechanism remains largely unknown. p16, as a well-known tumor suppressor, was also reported to suppress cell growth and migration, but with vague mechanism. In this study, we demonstrated atorvastatin represses cell proliferation and migration in vascular smooth muscle cells (VSMCs), which process is mediated by p16...
April 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28422052/folic-acid-reduces-tau-phosphorylation-by-regulating-pp2a-methylation-in-streptozotocin-induced-diabetic-mice
#5
Miaoyan Zheng, Chen Zou, Mengyue Li, Guowei Huang, Yuxia Gao, Huan Liu
High incidence rate of Alzheimer's disease (AD) is observed in patients with type 2 diabetes. Aggregated β-amyloid (Aβ) and hyperphosphorylated tau are the hallmarks of AD. Hyperphosphorylated tau has been detected in diabetic animals as well as in diabetic patients. Folates mediate the transfer of one carbon unit, required in various biochemical reactions. The effect of folate on tau phosphorylation in diabetic models still remains unknown. In this study, we investigated the effect and mechanism of folic acid on hyperphosphorylation of tau in streptozotocin (STZ)-induced diabetic mice...
April 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28421879/dna-methylation-mechanism-of-intracellular-zinc-deficiency-induced-injury-in-primary-hippocampal-neurons-in-the-rat-brain
#6
Cong-Cong He, Zi-Yu Wang, Kun Tian, Wei Liu, Yi-Bo Li, Yan Hong, Li-Xia Yu, Wei Pang, Yu-Gang Jiang, Yan-Qiang Liu
OBJECTIVE: To explore Zn(2+) deficiency-induced neuronal injury in relation to DNA methylation, providing valuable data and basic information for clarifying the mechanism of Zn(2+) deficiency-induced neuronal injury. METHODS: Cultured hippocampal neurons were exposed to the cell membrane-permeant Zn(2+) chelator N,N,N',N'-Tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) (2 μM), and to TPEN (2 μM) plus ZnSO4 (5 μM) for 24 hours. We analyzed intracellular Zn(2+) levels, neuronal viability, and protein/mRNA levels for DNA (cytosine-5) methyltransferase 1 (DNMT1), DNA (cytosine-5-) methyltransferase 3 alpha (DNMT3a), methyl CpG binding protein 2 (MeCP2), Brain-derived neurotrophic factor (BDNF), and growth arrest and DNA-damage-inducible, beta (GADD45b) in the treated neurons...
April 19, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28420163/beneficial-effects-of-melatonin-on-the-in-vitro-maturation-of-sheep-oocytes-and-its-relation-to-melatonin-receptors
#7
Xiuzhi Tian, Feng Wang, Lu Zhang, Changjiu He, Pengyun Ji, Jing Wang, Zhenzhen Zhang, Dongying Lv, Wusiman Abulizi, Xuguang Wang, Zhengxing Lian, Guoshi Liu
(1) Background: The binding sites of melatonin, as a multifunctional molecule, have been identified in human, porcine, and bovine samples. However, the binding sites and mechanisms of melatonin have not been reported in sheep; (2) Methods: Cumulus-oocyte complexes (COCs) were cultured in TCM-199 supplemented with melatonin at concentrations of 0, 10(-3), 10(-5), 10(-7), 10(-9), and 10(-11) M. Melatonin receptors (MT1 and MT2) were evaluated via immunofluorescence and Western blot. The effects of melatonin on cumulus cell expansion, nuclear maturation, embryo development, and related gene (GDF9, DNMT1, PTX3, HAS2, and EGFR) expression were investigated...
April 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28419930/design-synthesis-and-anticancer-potential-of-nsc-319745-hydroxamic-acid-derivatives-as-dnmt-and-hdac-inhibitors
#8
Zigao Yuan, Qinsheng Sun, Dan Li, Shuangshuang Miao, Shaopeng Chen, Lu Song, Chunmei Gao, Yuzong Chen, Chunyan Tan, Yuyang Jiang
DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) are important epigenetic targets during anticancer drug development. Recent study indicates that DNMT inhibitors and HDAC inhibitors display synergistic effects in certain cancers, therefore, development of molecules targeting both DNMT and HDAC is of therapeutic advantage against these cancers. Based on the structure of DNMT inhibitor NSC-319745 and the pharmacophore characteristics of HDAC inhibitors, a series of hydroxamic acid derivatives of NSC-319745 were designed and synthesized as DNMT and HDAC multifunctional inhibitors...
April 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28418087/traumatic-stress-induced-persistent-changes-in-dna-methylation-regulate-neuropeptide-y-expression-in-rat-jejunum
#9
S Sagarkar, S Mahajan, A G Choudhary, C D Borkar, D M Kokare, A J Sakharkar
BACKGROUND: Stress-induced chronic neuropsychiatric conditions such as anxiety are often co-morbid with gastrointestinal malfunctions. While we find enduring anxiety-like symptoms following minimal traumatic brain injury (MTBI) in rats, gastrointestinal consequences of MTBI remain elusive. METHODS: In this study, we examined the effects of MTBI on a major gut peptide, neuropeptide Y (NPY) and gut motility. DNA methylation was studied as a possible epigenetic mechanism operative in the regulation of NPY expression in the gut...
April 18, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28415607/thymoquinone-exerts-potent-growth-suppressive-activity-on-leukemia-through-dna-hypermethylation-reversal-in-leukemia-cells
#10
Jiuxia Pang, Na Shen, Fei Yan, Na Zhao, Liping Dou, Lai-Chu Wu, Christopher L Seiler, Li Yu, Ke Yang, Veronika Bachanova, Eric Weaver, Natalia Y Tretyakova, Shujun Liu
Thymoquinone (TQ), a bioactive constituent of the volatile oil of Monarda fistulosa and Nigella sativa, possesses cancer-specific growth inhibitory effects, but the underlying molecular mechanisms remain largely elusive. We propose that TQ curbs cancer cell growth through dysfunction of DNA methyltransferase 1 (DNMT1). Molecular docking analysis revealed that TQ might interact with the catalytic pocket of DNMT1 and compete with co-factor SAM/SAH for DNMT1 inhibition. In vitro inhibitory assays showed that TQ decreases DNMT1 methylation activity in a dose-dependent manner with an apparent IC50 of 30 nM...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414276/studying-the-association-between-sudden-hearing-loss-and-dna-n-methyltransferase-1-dnmt1-genetic-polymorphism
#11
Kübra Şeker Yıldız, Kasım Durmuş, Gonca Dönmez, Serdal Arslan, Emine Elif Altuntaş
OBJECTIVE: The aim of the present study was to investigate whether there was any relationship between some DNA N-methyltransferase 1 (DNMT1) polymorphisms and susceptibility to idiopathic sudden sensorineural hearing loss (ISSHL) in ISSHL patients. MATERIAL AND METHODS: We investigated 90 patients diagnosed with ISSHL and a control group composed of 75 age- and gender-matched healthy individuals. DNA was extracted from the blood samples by phenol-chloroform method...
April 17, 2017: Journal of International Advanced Otology
https://www.readbyqxmd.com/read/28408839/dnmt1-regulates-human-endometrial-carcinoma-cell-proliferation
#12
Xinjing Wang, Bilan Li
Endometrial carcinoma (EC) is the most common gynecologic malignancy, but the molecular events involved in the development and progression of EC remain unclear. This study aimed to investigate the role of DNA methyltransferase 1 (DNMT1), a member of DNA methyltransferases, in EC. AN3CA cells were transfected with DNMT1 siRNA. The proliferation, cell cycle, and apoptosis of AN3CA cells were evaluated by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. The expression of related genes was detected by polymerase chain reaction and Western blot analysis...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28406523/exposure-to-extrinsic-stressors-social-defeat-or-bisphenol-a-eliminates-sex-differences-in-dna-methyltransferase-expression-in-the-amygdala
#13
Emily C Wright, Sarah A Johnson, Rebecca Hao, Alex S Kowalczyk, Gian D Greenberg, Evelyn Ordoñes Sanchez, Abigail Laman-Maharg, Brian C Trainor, Cheryl S Rosenfeld
Chemical and psychological stressors can exert long lasting changes in brain function and behavior. Changes in DNA methylation have been shown to be an important mechanism mediating long lasting changes in neural function and behavior, especially for anxiety-like or stress responses. Here we examined the effects of either a social or chemical stressor on DNA methyltransferase (DNMT) gene expression in the amygdala, an important brain region modulating stress responses and anxiety. In adult California mice (Peromyscus californicus) that were naïve to social defeat, females had higher levels of Dnmt1 expression in punch samples of the central amygdala (CeA) than males...
April 12, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28401098/elevated-expression-of-dnmt1-is-associated-with-increased-expansion-and-proliferation-of-hematopoietic-stem-cells-co-cultured-with-human-mscs
#14
Moharram Ahmadnejad, Naser Amirizadeh, Roya Mehrasa, Ahmad Karkhah, Mahin Nikougoftar, Arezoo Oodi
BACKGROUND: Mesenchymal stem cells (MSCs) play an important role in hematopoietic stem cell (HSC) maintenance, proliferation, and apoptosis. DNA methyltransferase 1 (DNMT1) is considered an essential factor in the maintenance of HSCs in mammalian cells. Therefore, this study was conducted to evaluate the mRNA expression level of DNMT1 during cord blood (CB)-HSC ex vivo expansion with MSCs. METHODS: Ex vivo cultures of CB-HSCs were performed in three culture conditions for 7 days: cytokines, cytokines with MSCs, and only MSCs...
March 2017: Blood Research
https://www.readbyqxmd.com/read/28400476/gad1-upregulation-programs-aggressive-features-of-cancer-cell-metabolism-in-the-brain-metastatic-microenvironment
#15
Patricia M Schnepp, Dennis D Lee, Ian H Guldner, Treasa K O'Tighearnaigh, Erin N Howe, Bhavana Palakurthi, Kaitlyn E Eckert, Tiffany A Toni, Brandon L Ashfeld, Siyuan Zhang
The impact of altered amino acid metabolism on cancer progression is not fully understood. We hypothesized that a metabolic transcriptome shift during metastatic evolution is crucial for brain metastasis. Here we report a powerful impact in this setting caused by epigenetic upregulation of glutamate decarboxylase 1 (GAD1), a regulator of the GABA neurotransmitter metabolic pathway. In cell-based culture and brain metastasis models, we found that downegulation of the DNA methyltransferase DNMT1 induced by the brain microenvironment-derived clusterin resulted in decreased GAD1 promoter methylation and subsequent upregulation of GAD1 expression in brain metastatic tumor cells...
April 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/28399172/in-silico-design-of-the-first-dna-independent-mechanism-based-inhibitor-of-mammalian-dna-methyltransferase-dnmt1
#16
Vedran Miletić, Ivica Odorčić, Patrik Nikolić, Željko M Svedružić
BACKGROUND: We use our earlier experimental studies of the catalytic mechanism of DNA methyltransferases to prepare in silico a family of novel mechanism-based inhibitors of human Dnmt1. Highly specific inhibitors of DNA methylation can be used for analysis of human epigenome and for the creation of iPS cells. RESULTS: We describe a set of adenosyl-1-methyl-pyrimidin-2-one derivatives as novel mechanism-based inhibitors of mammalian DNA methyltransferase Dnmt1. The inhibitors have been designed to bind simultaneously in the active site and the cofactor site and thus act as transition-state analogues...
2017: PloS One
https://www.readbyqxmd.com/read/28398586/neonatal-inhibition-of-dna-methylation-alters-cell-phenotype-in-sexually-dimorphic-regions-of-the-mouse-brain
#17
M Mosley, J Weathington, L R Cortes, E Bruggeman, A Castillo-Ruiz, B Xue, N G Forger
Many of the best-studied neural sex differences relate to differences in cell number and are due to the hormonal control of developmental cell death. However, several prominent neural sex differences persist even if cell death is eliminated. We hypothesized that these may reflect cell phenotype "decisions" that depend on epigenetic mechanisms, such as DNA methylation. To test this, we treated newborn mice with the DNA methyltransferase (DNMT) inhibitor zebularine, or vehicle, and examined two sexually dimorphic markers at weaning...
April 7, 2017: Endocrinology
https://www.readbyqxmd.com/read/28398479/clinical-significance-of-mirna-host-gene-promoter-methylation-in-prostate-cancer
#18
Kristina Daniunaite, Monika Dubikaityte, Povilas Gibas, Arnas Bakavicius, Juozas Rimantas Lazutka, Albertas Ulys, Feliksas Jankevicius, Sonata Jarmalaite
Only a part of prostate cancer (PCa) patients has aggressive malignancy requiring adjuvant treatment after radical prostatectomy (RP). Biomarkers capable to predict biochemical PCa recurrence (BCR) after RP would significantly improve preoperative risk stratification and treatment decisions. MicroRNA (miRNA) deregulation has recently emerged as an important phenomenon in tumor development and progression, however, the mechanisms remain largely unstudied. In the present study, based on microarray profiling of DNA methylation in 9 pairs of PCa and noncancerous prostate tissues (NPT), host genes of miR-155-5p, miR-152-3p, miR-137, miR-31-5p, and miR-642a, -b were analyzed for promoter methylation in 129 PCa, 35 NPT, and 17 benign prostatic hyperplasia samples (BPH) and compared to the expression of mature miRNAs and their selected targets (DNMT1, KDM1A, and KDM5B)...
April 7, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28394581/dna-methyltransferases-demonstrate-reduced-activity-against-arabinosylcytosine-implications-for-epigenetic-instability-in-acute-myeloid-leukemia
#19
Christopher S Nabel, Jamie E DeNizio, Martin Carroll, Rahul M Kohli
Arabinosylcytosine (araC) is a mainstay in the initial treatment of acute myeloid leukemia (AML), although relapses are common. Given the recent recognition of altered DNA methylation patterns in relapsed AML, we considered whether araC, which acts by incorporation into DNA, could itself perturb methylation dynamics. To explore this possibility, we examined several DNA methyltransferases and find that araC embedded in DNA is consistently methylated with an efficiency diminished relative to that of deoxycytidine...
April 12, 2017: Biochemistry
https://www.readbyqxmd.com/read/28391715/curcumin-sensitizes-prostate-cancer-cells-to-radiation-partly-via-epigenetic-activation-of-mir-143-and-mir-143-mediated-autophagy-inhibition
#20
Jianbo Liu, Min Li, Yuewei Wang, Jianchao Luo
Curcumin has been reported as a radiosensitizer in prostate cancer. But the underlying mechanism is not well understood. In this study, we firstly assessed how curcumin affects the expression of miR-143/miR-145 cluster. Then, we investigated whether miR-143 is involved in regulation of radiosensitivity and its association with autophagy in prostate cancer cells. Our data showed that PC3, DU145 and LNCaP cells treated with curcumin had significantly restored miR-143 and miR-145 expression. Curcumin showed similar effect as 5-AZA-dC on reducing methylation of CpG dinucleotides in miR-143 promoter...
April 10, 2017: Journal of Drug Targeting
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