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https://www.readbyqxmd.com/read/28627705/targeting-the-pd-l1-dnmt1-axis-in-acquired-resistance-to-sorafenib-in-human-hepatocellular-carcinoma
#1
Jianhua Liu, Yahui Liu, Lingyu Meng, Kai Liu, Bai Ji
Molecule-targeted therapy, such as sorafenib, is one of the effectively therapeutic options for advanced hepatocellular carcinoma (HCC). However, acquired resistance to sorafenib has been found in some HCC patients, resulting in poor prognosis. It is reported that PD-L1 and DNA methyltransferases (DNMTs) contribute to drug resistance. In this study, by inducing sorafenib-resistant HCC cell lines, we investigated their molecular and functional characteristics. Our data indicated that highly upregulated DNMT1 was positively correlated with PD-L1 overexpression in sorafenib-resistant HCC cells...
June 14, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28602611/dna-methyltransferases-modulate-hepatogenic-lineage-plasticity-of%C3%A2-mesenchymal-stromal-cells
#2
Chien-Wei Lee, Wei-Chih Huang, Hsien-Da Huang, Yi-Hsiang Huang, Jennifer H Ho, Muh-Hwa Yang, Vincent W Yang, Oscar K Lee
The irreversibility of developmental processes in mammalian cells has been challenged by rising evidence that de-differentiation of hepatocytes occurs in adult liver. However, whether reversibility exists in mesenchymal stromal cell (MSC)-derived hepatocytes (dHeps) remains elusive. In this study, we find that hepatogenic differentiation (HD) of MSCs is a reversible process and is modulated by DNA methyltransferases (DNMTs). DNMTs are regulated by transforming growth factor β1 (TGFβ1), which in turn controls hepatogenic differentiation and de-differentiation...
June 1, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28583846/epigenetic-effects-of-inhibition-of-heat-shock-protein-90-hsp90-in-human-pancreatic-and-colon-cancer
#3
Ganji Purnachandra Nagaraju, Christina Wu, Neha Merchant, Zhengjia Chen, Gregory B Lesinski, Bassel F El-Rayes
Silencing of tumor suppressor and DNA repair genes through methylation plays a role in cancer development, growth and response to therapy in colorectal and pancreatic cancers. Heat shock protein 90 (HSP90) regulates transcription of DNA methyltransferase enzymes (DNMT). In addition, DNMTs are client proteins of HSP90. The aim of this study is to evaluate the effects of HSP90 inhibition on DNA methylation in colorectal and pancreatic cancer cell lines. Our data shows that inhibition of HSP90 using ganetespib resulted in downregulation of mRNA and protein expression of DNMT1, DNMT3A, and DNMT3B in HT-29 and MIA PaCa-2 cell lines...
June 3, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28574380/mthfr-gene-c677t-polymorphism-and-levels-of-dna-methyltrasferases-in-subclinical-hypothyroidism
#4
T Kvaratskhelia, E Kvaratskhelia, K Kankava, E Abzianidze
The aim of our study was to investigate the link between MTHFR gene C677T polymorphism and DNMTs levels in patients with Subclinical Hypothyroidism (SCH). In this study 19 adult patients with subclinical hypothyroidism and 19 healthy controls (mean age 31±5.5 and 33±5.1 years respectively) were recruited. All patients were diagnosed based on serum levels of TSH, FT4, anti-TG and anti-TPO antibodies. Written informed consents were obtained from all study subjects. Genomic DNA was extracted using Quick-DNA Universal Kit (Zymo Research, USA)...
April 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28560437/the-expression-of-dna-methyltransferases3a-is-specifically-downregulated-in-chorionic-villi-of-early-embryo-growth-arrest-cases
#5
Huating Gu, Jing Gao, Weiwei Guo, Yu Zhou, Qingnuan Kong
The aim of the present study was to investigate the expression pattern of four DNA methyltransferases (DNMT1, DNMT3A, DNMT3B and DNMT3L) in placenta chorionic villi of early embryo growth arrest patients. Chorionic villous specimens were obtained from 40 pregnant patients diagnosed with early embryo growth arrest and 40 healthy women who underwent selective pregnancy termination. Reverse transcription‑quantitative polymerase chain reaction, immunohistochemistry and western blot analysis were performed to characterize the mRNA and protein expression of DNMTs in chorionic villous cells...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28548080/discovery-of-first-in-class-reversible-dual-small-molecule-inhibitors-against-g9a-and-dnmts-in-hematological-malignancies
#6
Edurne San José-Enériz, Xabier Agirre, Obdulia Rabal, Amaia Vilas-Zornoza, Juan A Sanchez-Arias, Estibaliz Miranda, Ana Ugarte, Sergio Roa, Bruno Paiva, Ander Estella-Hermoso de Mendoza, Rosa María Alvarez, Noelia Casares, Victor Segura, José I Martín-Subero, François-Xavier Ogi, Pierre Soule, Clara M Santiveri, Ramón Campos-Olivas, Giancarlo Castellano, Maite Garcia Fernandez de Barrena, Juan Roberto Rodriguez-Madoz, Maria José García-Barchino, Juan Jose Lasarte, Matias A Avila, Jose Angel Martinez-Climent, Julen Oyarzabal, Felipe Prosper
The indisputable role of epigenetics in cancer and the fact that epigenetic alterations can be reversed have favoured development of epigenetic drugs. In this study, we design and synthesize potent novel, selective and reversible chemical probes that simultaneously inhibit the G9a and DNMTs methyltransferase activity. In vitro treatment of haematological neoplasia (acute myeloid leukaemia-AML, acute lymphoblastic leukaemia-ALL and diffuse large B-cell lymphoma-DLBCL) with the lead compound CM-272, inhibits cell proliferation and promotes apoptosis, inducing interferon-stimulated genes and immunogenic cell death...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28534825/a-novel-combination-of-withaferin-a-and-sulforaphane-inhibits-epigenetic-machinery-cellular-viability-and-induces-apoptosis-of-breast-cancer-cells
#7
Kendra J Royston, Neha Udayakumar, Kayla Lewis, Trygve O Tollefsbol
With cancer often classified as a disease that has an important epigenetic component, natural compounds that have the ability to regulate the epigenome become ideal candidates for study. Humans have a complex diet, which illustrates the need to elucidate the mechanisms of interaction between these bioactive compounds in combination. The natural compounds withaferin A (WA), from the Indian winter cherry, and sulforaphane (SFN), from cruciferous vegetables, have numerous anti-cancer effects and some report their ability to regulate epigenetic processes...
May 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28528402/impact-of-brown-rice-specific-%C3%AE-oryzanol-on-epigenetic-modulation-of-dopamine-d2-receptors-in-brain-striatum-in-high-fat-diet-induced-obesity-in-mice
#8
Chisayo Kozuka, Tadashi Kaname, Chigusa Shimizu-Okabe, Chitoshi Takayama, Masato Tsutsui, Masayuki Matsushita, Keiko Abe, Hiroaki Masuzaki
AIMS/HYPOTHESIS: Overeating of dietary fats causes obesity in humans and rodents. Recent studies in humans and rodents have demonstrated that addiction to fats shares a common mechanism with addiction to alcohol, nicotine and narcotics in terms of a dysfunction of brain reward systems. It has been highlighted that a high-fat diet (HFD) attenuates dopamine D2 receptor (D2R) signalling in the striatum, a pivotal regulator of the brain reward system, resulting in hedonic overeating. We previously reported that the brown rice-specific bioactive constituent γ-oryzanol attenuated the preference for an HFD via hypothalamic control...
May 20, 2017: Diabetologia
https://www.readbyqxmd.com/read/28513272/neuronal-dna-methyltransferases-epigenetic-mediators-between-synaptic-activity-and-gene-expression
#9
Gonca Bayraktar, Michael R Kreutz
DNMT3A and 3B are the main de novo DNA methyltransferases (DNMTs) in the brain that introduce new methylation marks to non-methylated DNA in postmitotic neurons. DNA methylation is a key epigenetic mark that is known to regulate important cellular processes in neuronal development and brain plasticity. Accumulating evidence disclosed rapid and dynamic changes in DNA methylation of plasticity-relevant genes that are important for learning and memory formation. To understand how DNMTs contribute to brain function and how they are regulated by neuronal activity is a prerequisite for a deeper appreciation of activity-dependent gene expression in health and disease...
May 1, 2017: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
https://www.readbyqxmd.com/read/28458013/aberrant-methylation-of-runx3-is-present-in-aflatoxin-b1-induced-transformation-of-the-l02r-cell-line
#10
Shan Wang, Zhini He, Daochuan Li, Bo Zhang, Miao Li, Wenxue Li, Wei Zhu, Xiumei Xing, Xiaowen Zeng, Qing Wang, Guanghui Dong, Yongmei Xiao, Wen Chen, Liping Chen
Chronic exposure to aflatoxin B1 (AFB1) is linked to the development of hepatocellular carcinoma (HCC). To identify differentially methylated genes involved in AFB1-induced cell transformation, we analyzed DNA methylation patterns in immortal human hepatocyte L02 cells expressing an oncogenic H-Ras allele (L02R cells) and AFB1-transformed L02R (L02RT-AFB1) cells by performing genome-wide methylation profiling. We treated L02R cells with 0.3μM AFB1 weekly and observed a transformed phenotype at the 17th week post-treatment...
June 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28443478/role-of-oxidative-stress-in-epigenetic-modification-in-endometriosis
#11
Fuminori Ito, Yuki Yamada, Aiko Shigemitsu, Mika Akinishi, Hiroko Kaniwa, Ryuta Miyake, Shoichiro Yamanaka, Hiroshi Kobayashi
Aberrant DNA methylation and histone modification are associated with an increased risk of reproductive disorders such as endometriosis. However, a cause-effect relationship between epigenetic mechanisms and endometriosis development has not been fully determined. This review provides current information based on oxidative stress in epigenetic modification in endometriosis. This article reviews the English-language literature on epigenetics, DNA methylation, histone modification, and oxidative stress associated with endometriosis in an effort to identify epigenetic modification that causes a predisposition to endometriosis...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28441774/brain-derived-neurotrophic-factor-mediated-perfluorooctane-sulfonate-induced-neurotoxicity-via-epigenetics-regulation-in-sk-n-sh-cells
#12
Xin-Xin Guo, Qing-Zhi He, Wu Li, Ding-Xin Long, Xiao-Yuan Pan, Cong Chen, Huai-Cai Zeng
Perfluorooctane sulfonate (PFOS), a new kind of persistent organic pollutant, is widely distributed in the environment and exists in various organisms, where it is also a neurotoxic compound. However, the potential mechanism of its neurotoxicity is still unclear. To examine the role of epigenetics in the neurotoxicity induced by PFOS, SK-N-SH cells were treated with different concentrations of PFOS or control medium (0.1% DMSO) for 48 h. The mRNA levels of DNA methyltransferases (DNMTs) and Brain-derived neurotrophic factor (BDNF), microRNA-16, microRNA-22, and microRNA-30a-5p were detected by Quantitative PCR (QPCR)...
April 24, 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
#13
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/28349196/decreased-mrna-expression-levels-of-dna-methyltransferases-type-1-and-3a-in-systemic-lupus-erythematosus
#14
Mariusz J Nawrocki, Dominik Majewski, Mariusz Puszczewicz, Paweł P Jagodziński
OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic relapsing autoimmune disease characterized by the presence of autoantibodies directed against nuclear antigens and by chronic inflammation. Although the etiology of SLE remains unclear, the influence of environment factors, which is largely reflected by the epigenetic mechanisms, with DNA methylation changes in particular, is generally considered as main players in the pathogenesis of SLE. We studied DNA methyltransferases' (DNMTs) type 1, 3A and 3B transcript levels in peripheral blood mononuclear cells from patients diagnosed with systemic lupus erythematosus and from the healthy control subjects...
May 2017: Rheumatology International
https://www.readbyqxmd.com/read/28338387/comparison-of-the-effects-of-curcumin-and-rg108-on-ngf-induced-pc-12%C3%A2-adh-cell-differentiation-and-neurite-outgrowth
#15
COMPARATIVE STUDY
Miriş Dikmen
DNA methyltransferases (DNMTs) are promising epigenetic targets for the development of novel drugs, especially for neurodegenerative disorders. In recent years, there has been increased interest in small molecules that can cross the blood-brain barrier for the treatment of neurodegenerative diseases. Therefore, comparing the neuronal differentiative effects of a natural compound curcumin and a synthetic small molecule RG108 was the aim of this study. The effects of curcumin and RG108 on neuronal differentiation and neurite outgrowth were investigated in the PC-12 Adh cell line...
April 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28336320/preliminary-research-on-dna-methylation-changes-during-murine-palatogenesis-induced-by-tcdd
#16
Chen Wang, Xin-Gang Yuan, Cui-Ping Liu, Sha-Na Zhai, Ding-Wen Zhang, Yue-Xian Fu
2,3,7,8-Tetrachlrodibenzo-p-dioxin (TCDD) has been shown to induce cleft palate through growth factor and receptor expression changes during palatogenesis. DNA methylation is an important epigenetic modification that can regulate gene expressions and may be involved in TCDD-induced cleft palate. In this study, we investigated the effects of TCDD on the global and CpG DNA methylation status and the expression levels of DNA methyltransferases (Dnmts) in palate tissue of fetal mice. Pregnant C57BL/6J mice were administered with corn oil or TCDD 28 μg/kg at gestation day 10...
February 12, 2017: Journal of Cranio-maxillo-facial Surgery
https://www.readbyqxmd.com/read/28323001/dna-methyltransferase-1-rs16999593-genetic-polymorphism-decreases-risk-in-patients-with-transposition-of-great-arteries
#17
Liming Lei, Haoming Lin, Shilong Zhong, Zhiwei Zhang, Jimei Chen, Xiyong Yu, Xiaoqing Liu, Cheng Zhang, Zhiqiang Nie, Jian Zhuang
Complete transposition of the great arteries (TGA) is the most frequent cyanotic heart defect diagnosed in neonates. However, the exact etiology of TGA is unknown. The aim of the present study was to assess the association of TGA pathogenesis with single nucleotide polymorphisms (SNPs) in DNA methyltransferases (DNMTs)-1 and 3a- in Chinese children. We genotyped 5 SNPs (rs16999593, rs16999358, and rs2228611 in DNMT1; and rs2276599 and rs2276598 in DNMT3A) in 206 patients with complete TGA and 252 healthy children...
June 5, 2017: Gene
https://www.readbyqxmd.com/read/28321157/hsa-mir-183-is-frequently-methylated-and-related-to-poor-survival-in-human-hepatocellular-carcinoma
#18
Sumadi Lukman Anwar, Till Krech, Britta Hasemeier, Elisa Schipper, Nora Schweitzer, Arndt Vogel, Hans Kreipe, Reena Buurman, Britta Skawran, Ulrich Lehmann
AIM: To screen clinically relevant microRNAs (miRNAs) silenced by DNA methylation in human hepatocellular carcinoma (HCC). METHODS: Knockdown of DNA methyltransferases (DNMTs) using siRNAs and miRNA profiling in HCC cell lines were performed to identify DNA hypermethylation-mediated miRNA downregulation. Confirmation using individual quantitative real-time PCR (qRT-PCR) assays was then performed followed by DNA methylation quantification at the promoter of the miRNA genes...
March 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28300471/decoupling-of-dna-methylation-and-activity-of-intergenic-line-1-promoters-in-colorectal-cancer
#19
Natasha Vafadar-Isfahani, Christina Parr, Lara E McMillan, Juliane Sanner, Zhao Yeo, Stephen Saddington, Oliver Peacock, Hazel A Cruickshanks, Richard R Meehan, Jonathan N Lund, Cristina Tufarelli
Hypomethylation of LINE-1 repeats in cancer has been proposed as the main mechanism behind their activation; this assumption, however, was based on findings from early studies that were biased toward young and transpositionally active elements. Here, we investigate the relationship between methylation of 2 intergenic, transpositionally inactive LINE-1 elements and expression of the LINE-1 chimeric transcript (LCT) 13 and LCT14 driven by their antisense promoters (L1-ASP). Our data from DNA modification, expression, and 5'RACE analyses suggest that colorectal cancer methylation in the regions analyzed is not always associated with LCT repression...
March 16, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28278502/kaempferol-modulates-dna-methylation-and-downregulates-dnmt3b-in-bladder-cancer
#20
Wei Qiu, Jun Lin, Yichen Zhu, Jian Zhang, Liping Zeng, Ming Su, Ye Tian
BACKGROUND: Genomic DNA methylation plays an important role in both the occurrence and development of bladder cancer. Kaempferol (Kae), a natural flavonoid that is present in many fruits and vegetables, exhibits potent anti-cancer effects in bladder cancer. Similar to other flavonoids, Kae possesses a flavan nucleus in its structure. This structure was reported to inhibit DNA methylation by suppressing DNA methyltransferases (DNMTs). However, whether Kae can inhibit DNA methylation remains unclear...
2017: Cellular Physiology and Biochemistry
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