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https://www.readbyqxmd.com/read/29159499/redistribution-of-cell-cycle-by-arsenic-trioxide-is-associated-with-demethylation-and-expression-changes-of-cell-cycle-related-genes-in-acute-promyelocytic-leukemia-cell-line-nb4
#1
Saeed Hassani, Ali Khaleghian, Shahin Ahmadian, Shaban Alizadeh, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
PML-RARα perturbs the normal epigenetic setting, which is essential to oncogenic transformation in acute promyelocytic leukemia (APL). Transcription induction and recruitment of DNA methyltransferases (DNMTs) by PML-RARα and subsequent hypermethylation are components of this perturbation. Arsenic trioxide (ATO), an important drug in APL therapy, concurrent with degradation of PML-RARα induces cell cycle change and apoptosis. How ATO causes cell cycle alteration has remained largely unexplained. Here, we investigated DNA methylation patterns of cell cycle regulatory genes promoters, the effects of ATO on the methylated genes and cell cycle distribution in an APL cell line, NB4...
November 20, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29156743/hepatitis-c-virus-core-overcomes-all-trans-retinoic-acid-induced-apoptosis-in-human-hepatoma-cells-by-inhibiting-p14-expression-via-dna-methylation
#2
Juri Kwak, Jung-Hye Choi, Kyung Lib Jang
All-trans retinoic acid (ATRA), the most biologically active metabolite of vitamin A, is known to induce p14 expression via promoter hypomethylation to activate the p14-MDM2-p53 pathway, which leads to activation of the p53-dependent apoptotic pathway and subsequent induction of apoptosis in human hepatoma cells. In the present study, we found that hepatitis C virus (HCV) Core derived from ectopic expression or HCV infection overcomes ATRA-induced apoptosis in p53-positive hepatoma cells. For this effect, HCV Core upregulated both protein levels and enzyme activities of DNA methyltransferase 1 (DNMT1), DNMT3a, and DNMT3b and thereby repressed p14 expression via promoter hypermethylation, resulting in inactivation of the pathway leading to p53 accumulation in the presence of ATRA...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155363/homocysteine-inhibits-endothelial-progenitor-cell-proliferation-via-dnmt1-mediated-hypomethylation-of-cyclin-a
#3
Hui-Ping Zhang, Yan-Hua Wang, Sheng-Chao Ma, Hui Zhang, An-Ning Yang, Xiao-Ling Yang, Ming-Hao Zhang, Jian-Min Sun, Yin-Ju Hao, Yi-Deng Jiang
Endothelial progenitor cells (EPCs) contribute to neovasculogenesis and reendothelialization of damaged blood vessels to maintain the endothelium. Dysfunction of EPCs is implicated in the pathogenesis of vascular injury induced by homocysteine (Hcy). We aimed to investigate the role of Cyclin A in Hcy-induced EPCs dysfunction and explore its molecular mechanism. In this study, by treatment of EPCs with Hcy, we found that the expression of Cyclin A mRNA and protein were significantly downregulated in a dose-dependent manner...
November 16, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29148180/dna-methylation-in-the-central-and-efferent-limbs-of-the-chemo-reflex-requires-carotid-body-neural-activity
#4
Jayasri Nanduri, Ying-Jie Peng, Ning Wang, Shakil A Khan, Gregg L Semenza, Nanduri R Prabhakar
Long-term exposure to intermittent hypoxia (LT-IH; 30 days), simulating blood O2 profiles during sleep apnea, has been shown to repress anti-oxidant enzyme (AOE) gene expression by DNA methylation in the carotid body (CB) reflex pathway, resulting in persistent elevation of plasma catecholamine levels and blood pressure. The present study examined the mechanisms by which LT-IH induces DNA methylation. Adult rats exposed to LT-IH showed elevated reactive oxygen species (ROS) in the CB, nucleus tractus solitarius (nTS) and rostroventrolateral medulla (RVLM) and adrenal medulla (AM), which represent the central and efferent limbs of the CB reflex, respectively...
November 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29147493/the-effect-of-the-ovarian-varicose-vein-on-the-dna-methylation-in-the-rat-s-oocyte
#5
Amirhossein Mohammadi, Bagher Minaei Zangi, Mahshid Delfan Azari, Rafieh Alizadeh, Mohammad Salehi, Erfan Daneshi, Mohammad Jafar Rezaei, Mehdi Abbasi
Objectives: We intended to determine whether the ovarian varicose which is one of the common etiologies of the pelvic congestion syndrome, has the ability to interfere with the DNA methylation reprogramming in the oocyte and thereby affect the oocyte quality or not. Materials and Methods: Varicose model was induced according to the Turner's method in the rats. Briefly, a 20-gauge needle was placed on the left renal vein and a thread was tied over both the needle and the renal vein medial to the insertion of the ovarian vein, and then the needle was removed...
October 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29145563/neuronal-dnmt1-deficiency-attenuates-diet-induced-obesity-in-mice
#6
Emily C Bruggeman, John T Garretson, Rui Wu, Hang Shi, Bingzhong Xue
Aberrant neuronal DNA methylation patterns have been implicated in the promotion of obesity development, but the role of neuronal DNA methyltransferases (Dnmts; enzymes that catalyze DNA methylation) in energy balance remains poorly understood. We investigated whether neuronal Dnmt1 regulates normal energy homeostasis and obesity development using a novel Dnmt1 knockout mouse model, Dnmt1fl/fl Synapsin1Cre (ND1KO), which specifically deletes Dnmt1 in neurons.Neuronal Dnmt1 deficiency reduced adiposity in chow-fed mice and attenuated obesity in HFD-fed male mice...
November 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/29137822/dnmt1-is-associated-with-cell-cycle-and-dna-replication-gene-sets-in-diffuse-large-b-cell-lymphoma
#7
Suet Kee Loo, Suzina Sheikh Ab Hamid, Mustaffa Musa, Kah Keng Wong
Dysregulation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) is associated with the pathogenesis of various types of cancer. It has been previously shown that DNMT1 is frequently expressed in diffuse large B-cell lymphoma (DLBCL), however its functions remain to be elucidated in the disease. In this study, we gene expression profiled (GEP) shRNA targeting DNMT1(shDNMT1)-treated germinal center B-cell-like DLBCL (GCB-DLBCL)-derived cell line (i.e. HT) compared with non-silencing shRNA (control shRNA)-treated HT cells...
October 9, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29137356/disruption-of-stat3-dnmt1-interaction-by-sh-i-14-induces-re-expression-of-tumor-suppressor-genes-and-inhibits-growth-of-triple-negative-breast-tumor
#8
Hyo Jin Kang, Yong Weon Yi, Shu-Jie Hou, Hee Jeong Kim, Yali Kong, Insoo Bae, Milton L Brown
Epigenetic regulation of gene expression is an emerging target to treat several human diseases including cancers. In cancers, expressions of many tumor suppressor genes are suppressed by hyper-methylation in their regulatory regions. Herein, we describe a novel carbazole SH-I-14 that decreased the level of the acetyl-STAT3 at the K685 residue. Mutation analysis revealed that SH-I-14 disrupted STAT3-DNMT1 interaction by removing acetyl group from K685 of STAT3. Finally, the inhibition of STAT3-DNMT1 interaction by SH-I-14 resulted in re-expression of tumor suppressor genes such as VHL and PDLIM4 through de-methylation of their promoter regions...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29131266/reactive-oxygen-species-downregulate-arid1a-expression-via-its-promoter-methylation-during-the-pathogenesis-of-endometriosis
#9
H Xie, P Chen, H-W Huang, L-P Liu, F Zhao
OBJECTIVE: Oxidative stress caused by reactive oxygen species (ROS) plays an important role in the pathogenesis of endometriosis. The gene AT-rich interactive domain 1A (ARID1A), is frequently down regulated and inactivated in endometriosis. This report is focused on the molecular mechanism of the correlation between oxidative stress and ARID1A gene expression in endometrial cell oxidative damage model. PATIENTS AND METHODS: In this study, the ARID1A gene expression level and its promoter methylation level were detected in 30 endometriosis and normal tissues...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29118325/the-mammalian-target-of-rapamycin-and-dna-methyltransferase-1-axis-mediates-vascular-endothelial-dysfunction-in-response-to-disturbed-flow
#10
Yun-Peng Zhang, Yi-Tao Huang, Tse-Shun Huang, Wei Pang, Juan-Juan Zhu, Yue-Feng Liu, Run-Ze Tang, Chuan-Rong Zhao, Wei-Juan Yao, Yi-Shuan Li, Shu Chien, Jing Zhou
The earliest atherosclerotic lesions preferentially develop in arterial regions experienced disturbed blood flow, which induces endothelial expression of pro-atherogenic genes and the subsequent endothelial dysfunction. Our previous study has demonstrated an up-regulation of DNA methyltransferase 1 (DNMT1) and a global hypermethylation in vascular endothelium subjected to disturbed flow. Here, we determined that DNMT1-specific inhibition in arterial wall ameliorates the disturbed flow-induced atherosclerosis through, at least in part, targeting cell cycle regulator cyclin A and connective tissue growth factor (CTGF)...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29117507/zingerone-protects-keratinocyte-stem-cells-from-uvb-induced-damage
#11
Jienny Lee, Sae Woong Oh, Seoung Woo Shin, Kyung-Woo Lee, Jae-Youl Cho, Jongsung Lee
The epidermis, the outermost layer of the skin, is a stratified epithelium that protects the body from the external environment. Keratinocyte stem cells (KSCs) are involved in epidermis homeostasis by maintaining epidermal integrity through a process of constant regeneration. Ultraviolet B (UVB) radiation is a major inducer of cellular damage in the epidermis. In this study, we investigated the effects of zingerone (a phenolic compound derived from spices) on UVB-induced cellular damage in KSCs. We found that zingerone significantly inhibited cellular senescence of KSCs in response to UVB irradiation...
November 5, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29117290/the-dna-methyltransferase-1-dnmt1-controls-the-shape-and-dynamics-of-migrating-poa-derived-interneurons-fated-for-the-murine-cerebral-cortex
#12
Daniel Pensold, Judit Symmank, Anne Hahn, Thomas Lingner, Gabriela Salinas-Riester, Bryan R Downie, Fabian Ludewig, Anne Rotzsch, Natja Haag, Nico Andreas, Katrin Schubert, Christian A Hübner, Tomas Pieler, Geraldine Zimmer
The proliferative niches in the subpallium generate a rich cellular variety fated for diverse telencephalic regions. The embryonic preoptic area (POA) represents one of these domains giving rise to the pool of cortical GABAergic interneurons and glial cells, in addition to striatal and residual POA cells. The migration from sites of origin within the subpallium to the distant targets like the cerebral cortex, accomplished by the adoption and maintenance of a particular migratory morphology, is a critical step during interneuron development...
December 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29109859/candidate-synthetic-lethality-partners-to-parp-inhibitors-in-the-treatment-of-ovarian-clear-cell-cancer
#13
Naoki Kawahara, Kenji Ogawa, Mika Nagayasu, Mai Kimura, Yoshikazu Sasaki, Hiroshi Kobayashi
Inhibitors of poly(ADP-ribose) polymerase (PARP) are new types of personalized treatment of relapsed platinum-sensitive ovarian cancer harboring BRCA1/2 mutations. Ovarian clear cell cancer (CCC), a subset of ovarian cancer, often appears as low-stage disease with a higher incidence among Japanese. Advanced CCC is highly aggressive with poor patient outcome. The aim of the present study was to determine the potential synthetic lethality gene pairs for PARP inhibitions in patients with CCC through virtual and biological screenings as well as clinical studies...
November 2017: Biomedical Reports
https://www.readbyqxmd.com/read/29100357/dnmt3b-overexpression-contributes-to-aberrant-dna-methylation-and-myc-driven-tumor-maintenance-in-t-all-and-burkitt-s-lymphoma
#14
Candace J Poole, Wenli Zheng, Atul Lodh, Aleksey Yevtodiyenko, Daniel Liefwalker, Honglin Li, Dean W Felsher, Jan van Riggelen
Aberrant DNA methylation is a hallmark of cancer. However, our understanding of how tumor cell-specific DNA methylation patterns are established and maintained is limited. Here, we report that in T-cell acute lymphoblastic leukemia (T-ALL) and Burkitt's lymphoma the MYC oncogene causes overexpression of DNA methyltransferase (DNMT) 1 and 3B, which contributes to tumor maintenance. By utilizing a tetracycline-regulated MYC transgene in a mouse T-ALL (EμSRα-tTA;tet-o-MYC) and human Burkitt's lymphoma (P493-6) model, we demonstrated that DNMT1 and DNMT3B expression depend on high MYC levels, and that their transcription decreased upon MYC-inactivation...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100015/an-endosirna-based-repression-mechanism-counteracts-transposon-activation-during-global-dna-demethylation-in-embryonic-stem-cells
#15
Rebecca V Berrens, Simon Andrews, Dominik Spensberger, Fátima Santos, Wendy Dean, Poppy Gould, Jafar Sharif, Nelly Olova, Tamir Chandra, Haruhiko Koseki, Ferdinand von Meyenn, Wolf Reik
Erasure of DNA methylation and repressive chromatin marks in the mammalian germline leads to risk of transcriptional activation of transposable elements (TEs). Here, we used mouse embryonic stem cells (ESCs) to identify an endosiRNA-based mechanism involved in suppression of TE transcription. In ESCs with DNA demethylation induced by acute deletion of Dnmt1, we saw an increase in sense transcription at TEs, resulting in an abundance of sense/antisense transcripts leading to high levels of ARGONAUTE2 (AGO2)-bound small RNAs...
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29099280/variant-histone-h2afv-reprograms-dna-methylation-during-early-zebrafish-development
#16
Bhavani Madakashira, Laura Corbett, Chi Zhang, Pier Paoli, John W Casement, Jelena Mann, Kirsten C Sadler, Derek A Mann
The DNA methylome is re-patterned during discrete phases of vertebrate development. In zebrafish, there are two waves of global DNA demethylation and re-methylation: the first occurs prior to gastrulation when the parental methylome is changed to the zygotic pattern and the second occurs after formation of the embryonic body axis, during organ specification. The occupancy of the histone variant H2A.Z and regions of DNA methylation are generally anti-correlated, and it has been proposed that H2A.Z restricts the boundaries of highly methylated regions...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29080797/modulations-of-dnmt1-and-hdac1-are-involved-in-the-ota-induced-cytotoxicity-and-apoptosis-in-vitro
#17
Yajiao Zhou, Fang Gan, Lili Hou, Xuan Zhou, Yassin Abdulrahim Adam Ibrahim, Kehe Huang
Ochratoxin A (OTA) as a fungal metabolite is reported to induce cytotoxicity and apoptosis through the mechanism of oxidative stress. Oxidative stress could induce the epigenetic enzymes modifications. However, whether epigenetic enzymes modifications are involved in OTA-induced cytotoxicity and apoptosis has not been reported until now. Therefore, the objectives of this study were to verify OTA-induced cytotoxicity and apoptosis and to investigate the potential role of epigenetic enzymes in OTA-induced cytotoxicity and apoptosis in PK15 cells...
November 2, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29075061/harmine-a-novel-dna-methyltransferase-1-inhibitor-in-the-leukemia-cell-line
#18
Arezoo Oodi, Hamed Norouzi, Naser Amirizadeh, Mahin Nikougoftar, Zahra Vafaie
DNA methylation followed by tumor suppressor gene repression plays a critical role in the leukemia development. So, DNA methyl transferase inhibitors have great importance in treatment of theses malignancies. Harmine, A beta carboline alkaloid derivative of Peganum harmala, had shown anti- proliferative effects on leukemic cell line. This study aimed to evaluate the effect of Harmine on DNMT1 (DNA methyl transferase 1) expression in a leukemic cell line. Cell proliferation and cell cycle analysis were studied in NB4 cell line after treatment with Harmine for 72 h...
December 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/29074164/defective-regulation-of-l1-endogenous-retroelements-in-primary-sjogren-s-syndrome-and-systemic-lupus-erythematosus-role-of-methylating-enzymes
#19
Clio P Mavragani, Adrianos Nezos, Irina Sagalovskiy, Surya Seshan, Kyriakos A Kirou, Mary K Crow
OBJECTIVE: To investigate whether altered DNA methylation contributes to the inappropriate expression of LINE-1 (L1) retroelements in primary Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE). METHODS: Minor salivary glands (MSG) were obtained from 42 patients with primary SS [23 without adverse predictors for lymphoma development (SS-low risk), 7 SS-high risk and 12 complicated by B-cell lymphoma (SS-lymphoma)] and 17 sicca controls (SC). Additionally, kidney biopsy specimens and PBMCs were obtained from 23 and 73 lupus patients, respectively...
October 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29074044/dnmt1-is-predictive-of-survival-and-associated-with-ki-67-expression-in-r-chop-treated-diffuse-large-b-cell-lymphomas
#20
Suet Kee Loo, Ewe Seng Ch'ng, Charles H Lawrie, María Arestin Muruzabal, Ayman Gaafar, María Puente Pomposo, Azlan Husin, Md Salzihan Md Salleh, Alison H Banham, Lars M Pedersen, Michael B Møller, Tina M Green, Kah Keng Wong
DNMT1 is a target of approved anti-cancer drugs including decitabine. However, the prognostic value of DNMT1 protein expression in R-CHOP-treated diffuse large B-cell lymphomas (DLBCLs) remains unexplored. Here we showed that DNMT1 was expressed in the majority of DLBCL cases (n = 209/230, 90.9%) with higher expression in germinal centre B-cell-like (GCB)-DLBCL subtype. Low and negative DNMT1 expression (20% cut-off, n = 33/230, 14.3%) was predictive of worse overall survival (OS; p < 0.001) and progression-free survival (PFS; p < 0...
October 23, 2017: Pathology
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