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https://www.readbyqxmd.com/read/28537931/the-network-of-dab2ip-mir-138-in-regulating-drug-resistance-of-renal-cell-carcinoma-associated-with-stem-like-phenotypes
#1
Eun-Jin Yun, Jiancheng Zhou, Chun-Jung Lin, Shan Xu, John Santoyo, Elizabeth Hernandez, Chih-Ho Lai, Ho Lin, Dalin He, Jer-Tsong Hsieh
Targeted therapy is a standard of care for metastatic renal cell carcinoma (RCC) but the response rate is not overwhelmed, which only prolongs a short survival of patients due to the onset of therapeutic resistance. Although the mechanisms are not fully understood, the presence of cancer initiating cells (CIC) may underlie the drug resistance. Nevertheless, identifying CIC phenotypes with its biomarkers in RCC appear to be diverse and controversial from many reports. In this study, we took a different approach to focus on the regulatory mechanism in RCC-CIC and unveil DAB2IP-mediated miR-138 expression that plays a critical role in modulating stem-like phenotypes in RCC via targeting the ABC transporter (ABCA13) as well as oncogenic histone methyltransferase EZH2 while down regulation of miR-138 gene expression in RCC is due to epigenetic gene silencing by DNA methyltransferase 1 (DNMT1)...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28524020/altered-gene-expression-of-epigenetic-modifying-enzymes-in-response-to-dietary-supplementation-with-linseed-oil
#2
Ran Li, Eveline M Ibeagha-Awemu
Recently we showed that 5% linseed oil (LSO) and 5% safflower oil (SFO) supplementation of cow's diets reduced milk fat yield by 30·38 and 32·42% respectively, accompanied by differential expression of genes and regulation by microRNAs (miRNA). This research communication addresses the hypothesis that epigenetic regulation could be involved in the observed milk fat reduction. Thus, this study investigated the gene expression pattern of major epigenetic modifying enzymes in response to dietary supplementation with LSO or SFO...
May 2017: Journal of Dairy Research
https://www.readbyqxmd.com/read/28515364/nicotinamide-metabolism-regulates-glioblastoma-stem-cell-maintenance
#3
Jinkyu Jung, Leo J Y Kim, Xiuxing Wang, Qiulian Wu, Tanwarat Sanvoranart, Christopher G Hubert, Briana C Prager, Lisa C Wallace, Xun Jin, Stephen C Mack, Jeremy N Rich
Metabolic dysregulation promotes cancer growth through not only energy production, but also epigenetic reprogramming. Here, we report that a critical node in methyl donor metabolism, nicotinamide N-methyltransferase (NNMT), ranked among the most consistently overexpressed metabolism genes in glioblastoma relative to normal brain. NNMT was preferentially expressed by mesenchymal glioblastoma stem cells (GSCs). NNMT depletes S-adenosyl methionine (SAM), a methyl donor generated from methionine. GSCs contained lower levels of methionine, SAM, and nicotinamide, but they contained higher levels of oxidized nicotinamide adenine dinucleotide (NAD+) than differentiated tumor cells...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28513652/an-electrochemiluminescence-assay-for-sensitive-detection-of-methyltransferase-activity-in-different-cancer-cells-by-hybridization-chain-reaction-coupled-with-a-g-quadruplex-hemin-dnazyme-biosensing-strategy
#4
Hui Zhang, Zhihui Guo, Huilei Dong, Hongfei Chen, Chenxin Cai
In this work, a highly sensitive electrochemiluminescence (ECL) assay was fabricated for the detection of human DNA (cytosine-5)-methyltransferase1 (DNMT1) activity in cancer cells. The ECL assay coupled hybridization chain reaction with a G-quadruplex/hemin DNAzyme biosensing strategy. The ECL intensity changes (ΔI) allowed detection of DNMT1 activity down to 0.09 U mL(-1), and ΔI was proportional to the logarithm of the activity of DNMT1 within the range of 1.0 to 30.0 U mL(-1) in buffer solution. It also showed high sensitivity to DNMT1 activity in A549 cells, with a detection limit of about 2 cells...
May 17, 2017: Analyst
https://www.readbyqxmd.com/read/28502886/hmga2-a-driver-of-inflammation-is-associated-with-hypermethylation-in-acute-liver-injury
#5
Huimin Huang, Haidi Li, Xin Chen, Yang Yang, Xiaofeng Li, Wanxia Li, Cheng Huang, Xiaoming Meng, Lei Zhang, Jun Li
Acute liver injury (ALI) is characteristic of abrupt hepatic dysfunction and inflammatory response. Activaion of Kupffer cells (KCs) plays a central role in the pathogenesis of ALI. Since the High Mobility Group A protein2 (HMGA2) occurs as a driver at critical stage of hepatocellular carcinoma, herein, we investigated the role of HMGA2 in macrophage activation during ALI. Our study found that the expression of HMGA2 decreased dramatically both in KCs isolated from the liver in mice with ALI and in LPS-induced RAW264...
May 11, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28496034/effect-of-perinatal-exposure-to-bisphenol-a-on-dna-methylation-and-histone-acetylation-in-cerebral-cortex-and-hippocampus-of-postnatal-male-mice
#6
Dhiraj Kumar, Mahendra Kumar Thakur
Bisphenol-A (BPA) is an estrogenic endocrine disruptor mostly used for the production of polycarbonate plastics and epoxy resins. Recently we have reported that perinatal BPA exposure impaired spatial memory through upregulation of synaptic proteins Neurexin1 and Neuroligin3 in male mice. As epigenetic mechanism is a key regulator of memory, we hypothesized that BPA might influence memory through epigenetic regulation of gene expression. Here we provide evidence that perinatal exposure to BPA decreased 5-mC DNA but increased histone H3 acetylation in cerebral cortex and hippocampus of postnatal 3 and 8 weeks male mice...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28491150/dynamic-silencing-of-somatic-l1-retrotransposon-insertions-reflects-the-developmental-and-cellular-contexts-of-their-genomic-integration
#7
Manoj Kannan, Jingfeng Li, Sarah E Fritz, Kathryn E Husarek, Jonathan C Sanford, Teresa L Sullivan, Pawan Kumar Tiwary, Wenfeng An, Jef D Boeke, David E Symer
BACKGROUND: The ongoing mobilization of mammalian transposable elements (TEs) contributes to natural genetic variation. To survey the epigenetic control and expression of reporter genes inserted by L1 retrotransposition in diverse cellular and genomic contexts, we engineered highly sensitive, real-time L1 retrotransposon reporter constructs. RESULTS: Here we describe different patterns of expression and epigenetic controls of newly inserted sequences retrotransposed by L1 in various somatic cells and tissues including cultured human cancer cells, mouse embryonic stem cells, and tissues of pseudofounder transgenic mice and their progeny...
2017: Mobile DNA
https://www.readbyqxmd.com/read/28490812/hdac3-regulates-dnmt1-expression-in-multiple-myeloma-therapeutic-implications
#8
T Harada, H Ohguchi, Y Grondin, S Kikuchi, M Sagawa, Y-T Tai, R Mazitschek, T Hideshima, K C Anderson
Epigenetic signaling pathways are implicated in tumorigenesis and therefore histone deacetylases (HDACs) represent novel therapeutic targets for cancers including multiple myeloma (MM). Although non-selective HDAC inhibitors show anti-MM activities, unfavorable side effects limit their clinical efficacy. Isoform- and/or class-selective HDAC inhibition offers the possibility to maintain clinical activity while avoiding adverse events attendant to broad non-selective HDAC inhibition. We have previously reported that HDAC3 inhibition, either by genetic knockdown or selective inhibitor BG45, abrogates MM cell proliferation...
May 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28489348/novel-curcumin-liposome-modified-with-hyaluronan-targeting-cd44-plays-an-anti-leukemic-role-in-acute-myeloid-leukemia-in-vitro-and-in-vivo
#9
Dan Sun, Jian-Kang Zhou, Linshu Zhao, Zhe-Yu Zheng, Jiao Li, Wenchen Pu, Shaoyang Liu, Xue-Sha Liu, Shu-Jun Liu, Yu Zheng, Yun Zhao, Yong Peng
Curcumin has been widely used as a food additive for centuries and has been recently explored for its anti-inflammatory and antitumor properties. Although curcumin is pharmacologically safe and efficacious to certain cancers, its role against acute myeloid leukemia (AML) still remains unclear, and it lacks clinical application due to low water solubility and low in vivo bioavailability. To address these issues, we developed a novel curcumin liposome modified with hyaluronan (HA-Cur-LPs) to specifically deliver curcumin to AML by targeting CD44 on AML cell surface...
May 10, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28484495/mitochondrial-dna-hypomethylation-is-a-biomarker-associated-with-induced-senescence-in-human-fetal-heart-mesenchymal-stem-cells
#10
Dehai Yu, Zhonghua Du, Lingling Pian, Tao Li, Xue Wen, Wei Li, Su-Jeong Kim, Jialin Xiao, Pinchas Cohen, Jiuwei Cui, Andrew R Hoffman, Ji-Fan Hu
Background. Fetal heart can regenerate to restore its normal anatomy and function in response to injury, but this regenerative capacity is lost within the first week of postnatal life. Although the specific molecular mechanisms remain to be defined, it is presumed that aging of cardiac stem or progenitor cells may contribute to the loss of regenerative potential. Methods. To study this aging-related dysfunction, we cultured mesenchymal stem cells (MSCs) from human fetal heart tissues. Senescence was induced by exposing cells to chronic oxidative stress/low serum...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28484249/dna-methyltransferase1-dnmt1-isoform3-methylates-mitochondrial-genome-and-modulates-its-biology
#11
Sunil Kumar Saini, Kailash Chandra Mangalhara, Gopinath Prakasam, R N K Bamezai
Here we demonstrate localization of the isoform3 of DNA Methyltransferase1 (DNMT1) enzyme to mitochondria, instead of isoform1 as reported earlier. The fused DNMT1-isoform1, reported earlier to localize in mitochondria, surprisingly showed its exclusive presence inside the nucleus after its ectopic expression; and failed to localize in mitochondria. On the other hand, ectopically expressed DNMT1-isoform3 targeted itself to mitochondria and subsequently methylated CpG regions in the mitochondrial genome. In addition, overexpression of DNMT1-isoform3 affected mitochondrial biology and regulated its function...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28480959/research-on-the-epigenetic-regulation-mechanism-of-the-ptpn6-gene-in-advanced-chronic-myeloid-leukaemia
#12
Xiaokun Zhang, Lin Yang, Xiaojun Liu, Ziyuan Nie, Xingzhe Wang, Yuxia Pan, Jianmin Luo
PTPN6, a tyrosine phosphatase protein, plays a negative role in cell signal transduction and is negatively correlated with tumour formation and growth. However, epigenetic regulation mechanism of the PTPN6 gene in advanced chronic myeloid leukaemia (CML) remains unclear. This study investigated bone marrow or blood samples from 44 CML patients and 10 healthy volunteers. KCL22 and K562 cells were cultured and treated with demethylation drugs and histone deacetylase inhibitors. Real time quantitative polymerase chain reaction (qPCR), methylation-specific PCR, bisulfite sequencing PCR, Western blotting, co-immunoprecipitation and chromatin immunoprecipitation (ChIP) was performed...
May 8, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28473984/a-meta-analysis-of-the-association-between-dnmt1-polymorphisms-and-cancer-risk
#13
REVIEW
Hao Li, Jing-Wei Liu, Li-Ping Sun, Yuan Yuan
Previous studies have examined the associations of DNA methyltransferase 1 (DNMT1) polymorphisms, including single nucleotide polymorphisms rs16999593 (T/C), rs2228611 (G/A), and rs2228612 (A/G), with cancer risk. However, the results are inconclusive. The aim of this meta-analysis is to elucidate the associations between DNMT1 polymorphisms and cancer susceptibility. The PubMed, Embase, Web of Science, and Chinese National Knowledge Infrastructure databases were searched systematically to identify potentially eligible reports...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28472596/reciprocal-regulation-between-mir-148a-152-and-dna-methyltransferase-1-is-associated-with-hyperhomocysteinemia-accelerated-atherosclerosis
#14
Anning Yang, Yue Sun, Yuan Gao, Songhao Yang, Caiyan Mao, Ning Ding, Mei Deng, Yanhua Wang, Xiaoling Yang, Yuexia Jia, Huiping Zhang, Yideng Jiang
DNA methyltransferase 1 (DNMT1) and miRNAs are both important regulators of gene expression that have been implicated in the pathogenesis of atherosclerosis. This study was designed to elucidate the potential interaction between DNMT1 and miRNAs in the context of hyperhomocysteinemia (HHcy)-related atherosclerosis. In the aorta of ApoE(-/-) mice fed a high methionine diet, increased expression of miR-148a/152, with decreased DNMT1 mRNA and protein levels, was detected. Similar changes were observed in cultured foam cells stimulated with homocysteine...
May 4, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28470094/dna-methylation-controls-unmethylated-transcription-start-sites-in-the-genome-in-trans
#15
David Cheishvili, Steffan Christiansen, Rebecca Stochinsky, Anne-Sophie Pepin, Daniel M Sapozhnikov, Rudy Zhou, Lauren Schmeltzer, Sergey Dymov, Moshe Szyf
AIM: DNA methylation downregulates transcription. However, a large number of genes, which are unmethylated in the promoter region, are inactive. We tested the hypothesis that these genes are regulated by DNA methylation of upstream regulators. METHODS: We inhibited DNMT1 with 5-aza-2'-deoxycytidine or depleted it with shRNA to map the transcription initiation positions controlled by DNMT1 using ChIPseq with RNApolIIser5 antibody. Ingenuity pathway analysis identified potential methylated upstream regulators...
May 4, 2017: Epigenomics
https://www.readbyqxmd.com/read/28465359/elevated-foxg1-and-sox2-in-glioblastoma-enforces-neural-stem-cell-identity-through-transcriptional-control-of-cell-cycle-and-epigenetic-regulators
#16
Harry Bulstrode, Ewan Johnstone, Maria Angeles Marques-Torrejon, Kirsty M Ferguson, Raul Bardini Bressan, Carla Blin, Vivien Grant, Sabine Gogolok, Ester Gangoso, Sladjana Gagrica, Christine Ender, Vassiliki Fotaki, Duncan Sproul, Paul Bertone, Steven M Pollard
Glioblastoma multiforme (GBM) is an aggressive brain tumor driven by cells with hallmarks of neural stem (NS) cells. GBM stem cells frequently express high levels of the transcription factors FOXG1 and SOX2. Here we show that increased expression of these factors restricts astrocyte differentiation and can trigger dedifferentiation to a proliferative NS cell state. Transcriptional targets include cell cycle and epigenetic regulators (e.g., Foxo3, Plk1, Mycn, Dnmt1, Dnmt3b, and Tet3). Foxo3 is a critical repressed downstream effector that is controlled via a conserved FOXG1/SOX2-bound cis-regulatory element...
May 2, 2017: Genes & Development
https://www.readbyqxmd.com/read/28463515/rational-design-of-bisubstrate-type-analogues-as-inhibitors-of-dna-methyltransferases-in-cancer-cells
#17
Ludovic Halby, Yoann Menon, Elodie Rilova, Dany Pechalrieu, Véronique Masson, Celine Faux, Mohamed Amine Bouhlel, Marie-Hélène David-Cordonnier, Natacha Novosad, Yannick Aussagues, Arnaud Samson, Laurent Lacroix, Fréderic Ausseil, Laurence Fleury, Dominique Guianvarc'h, Clotilde Ferroud, Paola B Arimondo
Aberrant DNA hypermethylation of promoter of tumor suppressor genes is commonly observed in cancer, and its inhibition by small molecules is promising for their reactivation. Here we designed bisubstrate analogues-based inhibitors, by mimicking each substrate, the S-adenosyl-l-methionine and the deoxycytidine, and linking them together. This approach resulted in quinazoline-quinoline derivatives as potent inhibitors of DNMT3A and DNMT1, some showing certain isoform selectivity. We highlighted the importance of (i) the nature and rigidity of the linker between the two moieties for inhibition, as (ii) the presence of the nitrogen on the quinoline group, and (iii) of a hydrophobic group on the quinazoline...
May 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28463020/treatment-of-donor-cells-and-reconstructed-embryos-with-a-combination-of-trichostatin-a-and-5-aza-2-deoxycytidine-improves-the-developmental-competence-and-quality-of-buffalo-embryos-produced-by-handmade-cloning-and-alters-their-epigenetic-status-and-gene-expression
#18
Monika Saini, Naresh L Selokar, Himanshu Agrawal, Suresh Kumar Singla, Manmohan Singh Chauhan, Radheysham S Manik, Prabhat Palta
The application of cloning technology on a large scale is limited by very low offspring rate primarily due to aberrant or incomplete epigenetic reprogramming. Trichostatin A (TSA), a histone deacetylase inhibitor, and 5-aza-2'-deoxycytidine (5-aza-dC), an inhibitor of DNA methyltransferases, are widely used for altering the epigenetic status of cloned embryos. We optimized the doses of these epigenetic modifiers for production of buffalo embryos by handmade cloning and examined whether combined treatment with these epigenetic modifiers offered any advantage over treatment with the individual epigenetic modifier...
May 2, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28462005/inhibitors-of-dna-methylation-support-tgf-%C3%AE-1-induced-il11-expression-in-gingival-fibroblasts
#19
Irina-Georgeta Sufaru, Gabriel Beikircher, Andreas Weinhaeusel, Reinhard Gruber
PURPOSE: Oral wound healing requires gingival fibroblasts to respond to local growth factors. Epigenetic silencing through DNA methylation can potentially decrease the responsiveness of gingival fibroblasts to local growth factors. In this study, our aim was to determine whether the inhibition of DNA methylation sensitized gingival fibroblasts to transforming growth factor-β1 (TGF-β1). METHODS: Gingival fibroblasts were exposed to 5-aza-2'-deoxycytidine (5-aza), a clinically approved demethylating agent, before stimulation with TGF-β1...
April 2017: Journal of Periodontal & Implant Science
https://www.readbyqxmd.com/read/28459455/dna-sequence-homology-induces-cytosine-to-thymine-mutation-by-a-heterochromatin-related-pathway-in-neurospora
#20
Eugene Gladyshev, Nancy Kleckner
Most eukaryotic genomes contain substantial amounts of repetitive DNA organized in the form of constitutive heterochromatin and associated with repressive epigenetic modifications, such as H3K9me3 and C5 cytosine methylation (5mC). In the fungus Neurospora crassa, H3K9me3 and 5mC are catalyzed, respectively, by a conserved SUV39 histone methyltransferase, DIM-5, and a DNMT1-like cytosine methyltransferase, DIM-2. Here we show that DIM-2 can also mediate repeat-induced point mutation (RIP) of repetitive DNA in N...
May 1, 2017: Nature Genetics
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