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Methyltransferase

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https://www.readbyqxmd.com/read/29150792/correlation-between-mgmt-promoter-methylation-and-response-to-temozolomide-based-therapy-in-neuroendocrine-neoplasms-an-observational-retrospective-multicenter-study
#1
Davide Campana, Thomas Walter, Sara Pusceddu, Fabio Gelsomino, Emmanuelle Graillot, Natalie Prinzi, Andrea Spallanzani, Michelangelo Fiorentino, Marc Barritault, Filippo Dall'Olio, Nicole Brighi, Guido Biasco
PURPOSE: Temozolomide (TEM) based therapy has been reported being effective in the treatment of metastatic neuroendocrine neoplasms (NEN), with response rates ranging from 30 to 70%. Among patients affected by advanced glioblastoma or melanoma and treated with TEM, loss of tumoral O6-methylguanine DNA methyltransferase (MGMT) is correlated with improved survival. In NEN patients, the role of MGMT deficiency in predicting clinical outcomes of TEM treatment is still under debate. METHODS: In this study we evaluated 95 patients with advanced NENs undergoing treatment with TEM-based therapy...
November 17, 2017: Endocrine
https://www.readbyqxmd.com/read/29148585/arsenite-downregulates-h3k4-trimethylation-and-h3k9-dimethylation-during-transformation-of-human-bronchial-epithelial-cells
#2
Wei Tu, Yin Liu, Chengfeng Xie, Xue Zhou
Arsenic is an established human carcinogen but with weak mutagenic activity. The mechanisms of arsenic-induced carcinogenesis are not well understood. In the present study, we investigated the role of histone methylation in transformation of human bronchial epithelial (BEAS-2B) cells. After 16 weeks' exposure, cells were transformed by 0.1, 0.5 and 1 μm arsenite. Global trimethylated H3K4 (H3K4me3) was decreased by 0.1 μm arsenite at 12 weeks, and 0.5 and 1 μm arsenite at 8, 12 and 16 weeks, which could be attributed to reduced histone methyltransferase activities, increased histone demethylase (HDM) activities as well as increased protein levels of H3K4 demethylase KDM5A...
November 17, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29148015/clinical-performance-and-utility-of-a-nnmt-based-urine-test-for-bladder-cancer
#3
Valentina Pozzi, Giulia Di Ruscio, Davide Sartini, Roberto Campagna, Riccardo Seta, Paola Fulvi, Alexia Vici, Giulio Milanese, Gabriele Brandoni, Andrea B Galosi, Rodolfo Montironi, Monia Cecati, Monica Emanuelli
BACKGROUND: Bladder cancer (BC) represents the most common neoplasm of the urinary tract. Although cystoscopy and urine cytology represent the gold standard methods to monitor BC, both procedures have limitations. Therefore, the identification of reliable biomarkers for early and noninvasive detection of BC is urgently required. METHODS: In this study, we analyzed nicotinamide N-methyltransferase (NNMT) expression in urine samples from 55 BC patients and 107 controls, using real-time polymerase chain reaction (PCR)...
November 11, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/29147863/prognostic-relevance-of-programmed-cell-death-ligand-1-expression-in-glioblastoma
#4
Kyu Sang Lee, Kyoungyul Lee, Sumi Yun, Seyoung Moon, Yujun Park, Jung Ho Han, Chae-Yong Kim, Hye Seung Lee, Gheeyoung Choe
The aim of this study was to determine the clinicopathological significance of programmed cell death ligand 1 (PD-L1) expression in glioblastoma (GBM). In a retrospective cohort of 115 consecutive patients with GBM, PD-L1 expression was determined using immunohistochemistry (IHC). Membranous and fibrillary PD-L1 staining of any intensity in > 5% neoplastic cells and tumour infiltrating immune cells (TIIs) was considered positive staining. In addition, isocitrate dehydrogenase-1 (IDH-1) (R132H) expression and cluster of differentiation 3 (CD3)-positive T-cell infiltration were investigated using IHC...
November 16, 2017: Journal of Neuro-oncology
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/29147491/augmented-expression-levels-of-lncrnas-eccebpa-and-uca1-in-gastric-cancer-tissues-and-their-clinical-significance
#6
Mojdeh Nasrollahzadeh-Khakiani, Modjtaba Emadi-Baygi, Parvaneh Nikpour
Objectives: As the second cause of cancer death, gastric cancer (GC) is one of the eminent dilemmas all over the world, therefore investigating the molecular mechanisms involved in this cancer is pivotal. Unrestricted proliferation is one of the characteristics of cancerous cells, which is due to deficiency in cell regulatory systems. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of the epigenome. lncRNA extra coding CEBPA (ecCEBPA) is involved in DNA methylation...
October 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29147133/allopurinol-in-combination-with-thiopurine-induces-mucosal-healing-and-improves-clinical-and-metabolic-outcomes-in-ibd
#7
Brigitte Moreau, Pierre Clement, Yves Theoret, Ernest G Seidman
Background: Thiopurines, azathioprine (AZA) and 6-mercaptopurine (6-MP) are common maintenance medications for inflammatory bowel disease (IBD). Excessive methylation via thiopurine methyltransferase (TPMT) frequently causes therapeutic failure. Allopurinol reduces excessive 6-methyl-mercaptopurine (6-MMP) while enhancing 6-thioguanine (6-TGN) levels. The aim of this study was to evaluate clinical, metabolic and endoscopic impact of allopurinol in combination with low-dose thiopurine in IBD...
November 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/29146735/reduced-dnmt3a-increases-gdf5-expression-with-suppressed-satellite-cell-differentiation-and-impaired-skeletal-muscle-regeneration
#8
Yukino Hatazawa, Yusuke Ono, Yuma Hirose, Sayaka Kanai, Nobuharu L Fujii, Shuichi Machida, Ichizo Nishino, Takahiko Shimizu, Masaki Okano, Yasutomi Kamei, Yoshihiro Ogawa
DNA methylation is an epigenetic mechanism regulating gene expression. In this study, we observed that DNA methyltransferase 3a (Dnmt3a) expression is decreased after muscle atrophy. We made skeletal muscle-specific Dnmt3a knockout mice (Dnmt3a-KO mice). The regeneration capacity after muscle injury was markedly decreased in Dnmt3a-KO mice. Diminished mRNA and protein expression of Dnmt3a were observed in skeletal muscles as well as in satellite cells, which are important for muscle regeneration, in Dnmt3a-KO mice...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29146598/structural-analyses-unravel-the-molecular-mechanism-of-cyclic-di-gmp-regulation-of-bacterial-chemotaxis-via-a-pilz-adaptor-protein
#9
Xin-Fu Yan, Lingyi Xin, Jackie Tan Yen, Yukai Zeng, Shengyang Jin, Qing Wei Cheang, Rachel Andrea Chea Yuen Fong, Keng-Hwee Chiam, Zhao-Xun Liang, Yong-Gui Gao
The bacterial second messenger cyclic di-GMP (c-di-GMP) has emerged as a prominent mediator of bacterial physiology, motility and pathogenicity. Cdi-GMP often regulates the function of its protein targets through a unique mechanism that involves a discrete PilZ adaptor protein. However, the molecular mechanism in c-di-GMP-mediated protein regulation is unclear. Here, we present the structure of the PilZ adaptor protein MapZ co-crystallized in complex with c-di-GMP and its protein target CheR1, a chemotaxis-regulating methyltransferase in Pseudomonas aeruginosa This co-crystal structure, together with the structure of free CheR1, revealed that the binding of c-di-GMP induces dramatic structural changes in MapZ that are crucial for CheR1 binding...
November 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29146582/elucidation-of-the-two-h3k36me3-histone-methyltransferases-set2-and-ash1-in-fusarium-fujikuroi-unravels-their-different-chromosomal-targets-and-a-major-impact-of-ash1-on-genome-stability
#10
Slavica Janevska, Leonie Baumann, Christian M K Sieber, Martin Münsterkötter, Jonas Ulrich, Jörg Kämper, Ulrich Güldener, Bettina Tudzynski
In this work, we present a comprehensive analysis of the H3K36 histone methyltransferases Set2 and Ash1 in the filamentous ascomycete Fusarium fujikuroi In Saccharomyces cerevisiae, one single methyltransferase, Set2, confers all H3K36 methylation, while there are two members of the Set2 family in filamentous fungi, and even more H3K36 methyltransferases in higher eukaryotes. Whereas the yeast Set2 homolog has been analyzed in fungi previously, the second member of the Set2 family, designated Ash1, has not been described for any filamentous fungus...
November 16, 2017: Genetics
https://www.readbyqxmd.com/read/29145563/neuronal-dnmt1-deficiency-attenuates-diet-induced-obesity-in-mice
#11
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/29145444/inhibition-of-the-h3k9-methyltransferase-g9a-attenuates-oncogenicity-and-activates-the-hypoxia-signaling-pathway
#12
Jolene Caifeng Ho, Lissa Nurrul Abdullah, Qing You Pang, Sudhakar Jha, Edward Kai-Hua Chow, Henry Yang, Hiroyuki Kato, Lorenz Poellinger, Jun Ueda, Kian Leong Lee
Epigenetic mechanisms play important roles in the regulation of tumorigenesis, and hypoxia-induced epigenetic changes may be critical for the adaptation of cancer cells to the hypoxic microenvironment of solid tumors. Previously, we showed that loss-of-function of the hypoxia-regulated H3K9 methyltransferase G9A attenuates tumor growth. However, the mechanisms by which blockade of G9A leads to a tumor suppressive effect remain poorly understood. We show that G9A is highly expressed in breast cancer and is associated with poor patient prognosis, where it may function as a potent oncogenic driver...
2017: PloS One
https://www.readbyqxmd.com/read/29144405/genomic-analysis-of-the-asmt-gene-family-in-solanum-lycopersicum
#13
Weicheng Liu, Dake Zhao, Chunfang Zheng, Chen Chen, Xin Peng, Yuan Cheng, Hongjian Wan
Acetylserotonin methyltransferase (ASMT) is the last enzyme of melatonin biosynthesis and may play a rate-limiting role in the melatonin production of plants. In this study, systematic analysis of the ASMT gene family in tomato (Solanum lycopersicum Mill) has been presented by the integration of the structural features, phylogenetic relationships, exon/intron configuration, and expression profile during growth and development, as well as biotic stresses. The results revealed that the tomato genome encoded a minimum of 14 members, containing three probable encoded pseudogenes...
November 16, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29143344/down-regulation-of-p16-and-mgmt-promotes-the-anti-proliferative-and-pro-apoptotic-effects-of-5-aza-dc-and-radiation-on-cervical-cancer-cells
#14
Guan-di Chen, De-Ying Qian, Zhi-Gang Li, Ge-Ying Fan, Ke-Li You, Yi-Long Wu
Cervical cancer is one of the most common malignancies of the female reproductive system. Therefore, it is critical to investigate the molecular mechanisms involved in the development and progression of cervical cancer. In this study, we stimulated cervical cancer cells with 5-aza-2'-deoxycytidine (5-Aza-dC) and found that this treatment inhibited cell proliferation and induced apoptosis; additionally, methylation of p16 and O-6-methylguanine-DNA methyltransferase (MGMT) was reversed, although their expression was suppressed...
November 15, 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29142304/maternal-exposure-to-iodine-excess-throughout-pregnancy-and-lactation-induces-hypothyroidism-in-adult-male-rat-offspring
#15
Caroline Serrano-Nascimento, Rafael Barrera Salgueiro, Thiago Pantaleão, Vânia Maria Corrêa da Costa, Maria Tereza Nunes
This study aimed to investigate the consequences of maternal exposure to iodine excess (IE; 0.6 mg NaI/L) throughout pregnancy and lactation on the hypothalamus-pituitary-thyroid axis of the male offspring in adulthood. Maternal IE exposure increased hypothalamic Trh mRNA expression and pituitary Tsh expression and secretion in the adult male offspring. Moreover, the IE-exposed offspring rats presented reduced thyroid hormones levels, morphological alterations in the thyroid follicles, increased thyroid oxidative stress and decreased expression of thyroid differentiation markers (Tshr, Nis, Tg, Tpo, Mct8) and thyroid transcription factors (Nkx2...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29142071/chromatin-histone-modifications-and-rigidity-affect-nuclear-morphology-independent-of-lamins
#16
Andrew D Stephens, Patrick Z Liu, Edward J Banigan, Luay M Almassalha, Vadim Backman, Stephen A Adam, Robert D Goldman, John F Marko
Nuclear shape and architecture influence gene localization, mechanotransduction, transcription, and cell function. Abnormal nuclear morphology and protrusions termed "blebs" are diagnostic markers for many human afflictions including heart disease, aging, progeria, and cancer. Nuclear blebs are associated with both lamin and chromatin alterations. A number of prior studies suggest that lamins dictate nuclear morphology, but the contributions of altered chromatin compaction remain unclear. We show that chromatin histone modification state dictates nuclear rigidity, and modulating it is sufficient to both induce and suppress nuclear blebs...
November 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29142068/pharmacologic-inhibition-of-the-menin-mll-interaction-leads-to-transcriptional-repression-of-peg10-and-blocks-hepatocellular-carcinoma
#17
Katarzyna Kempinska, Bhavna Malik, Dmitry Borkin, Szymon Klossowski, Shirish Shukla, Hongzhi Miao, Jingya Wang, Tomasz Cierpicki, Jolanta Grembecka
Hepatocellular carcinoma (HCC) accounts for ~85% of malignant liver tumors and results in 600,000 deaths each year, emphasizing the need for new therapies. Upregulation of menin was reported in HCC patients and high levels of menin correlate with poor patient prognosis. The protein-protein interaction between menin and histone methyltransferase Mixed Lineage Leukemia 1 (MLL1) plays an important role in the development of HCC, implying that pharmacologic inhibition of this interaction could lead to new therapeutic strategy for the HCC patients...
November 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29141164/lomustine-and-bevacizumab-in-progressive-glioblastoma
#18
Wolfgang Wick, Thierry Gorlia, Martin Bendszus, Martin Taphoorn, Felix Sahm, Inga Harting, Alba A Brandes, Walter Taal, Julien Domont, Ahmed Idbaih, Mario Campone, Paul M Clement, Roger Stupp, Michel Fabbro, Emilie Le Rhun, Francois Dubois, Michael Weller, Andreas von Deimling, Vassilis Golfinopoulos, Jacoline C Bromberg, Michael Platten, Martin Klein, Martin J van den Bent
BACKGROUND: Bevacizumab is approved for the treatment of patients with progressive glioblastoma on the basis of uncontrolled data. Data from a phase 2 trial suggested that the addition of bevacizumab to lomustine might improve overall survival as compared with monotherapies. We sought to determine whether the combination would result in longer overall survival than lomustine alone among patients at first progression of glioblastoma. METHODS: We randomly assigned patients with progression after chemoradiation in a 2:1 ratio to receive lomustine plus bevacizumab (combination group, 288 patients) or lomustine alone (monotherapy group, 149 patients)...
November 16, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29140247/ddm1-and-lsh-remodelers-allow-methylation-of-dna-wrapped-in-nucleosomes
#19
David B Lyons, Daniel Zilberman
Cytosine methylation regulates essential genome functions across eukaryotes, but the fundamental question of whether nucleosomal or naked DNA is the preferred substrate of plant and animal methyltransferases remains unresolved. Here, we show that genetic inactivation of a single DDM1/Lsh family nucleosome remodeler biases methylation toward inter-nucleosomal linker DNA in Arabidopsis thaliana and mouse. We find that DDM1 enables methylation of DNA bound to the nucleosome, suggesting that nucleosome-free DNA is the preferred substrate of eukaryotic methyltransferases in vivo...
November 15, 2017: ELife
https://www.readbyqxmd.com/read/29140168/revisiting-the-roles-of-tobamovirus-replicase-complex-proteins-in-viral-replication-and-silencing-suppression
#20
Nachelli Malpica-López, Rajendran Rajeswaran, Daria Beknazariants, Jonathan Seguin, Victor Golyaev, Laurent Farinelli, Mikhail M Pooggin
Tobamoviral replicase possesses an RNA-dependent RNA polymerase (RDR) domain and is translated from genomic (g)RNA via a stop codon readthrough mechanism at a one-to-ten ratio relative to a shorter protein lacking the RDR domain. The two proteins share methyltransferase and helicase domains and form a heterodimer implicated in gRNA replication. The shorter protein is also implicated in suppressing RNA silencing-based antiviral defenses. Using a stop codon mutant of Oilseed rape mosaic tobamovirus (ORMV), we demonstrate that the readthrough replicase (p182) is sufficient for gRNA replication and for subgenomic RNA transcription during systemic infection in Nicotiana benthamiana and Arabidopsis thaliana...
November 15, 2017: Molecular Plant-microbe Interactions: MPMI
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