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https://www.readbyqxmd.com/read/28634614/detection-of-the-circulating-tumor-dnas-in-angioimmunoblastic-t-cell-lymphoma
#1
Mamiko Sakata-Yanagimoto, Rie Nakamoto-Matsubara, Daisuke Komori, Tran B Nguyen, Keiichiro Hattori, Toru Nanmoku, Takayasu Kato, Naoki Kurita, Yasuhisa Yokoyama, Naoshi Obara, Yuichi Hasegawa, Atsushi Shinagawa, Shigeru Chiba
Recent genetic studies identified that the disease-specific G17V RHOA mutation, together with mutations in TET2, DNMT3A, and IDH2, is a hallmark of angioimmunoblastic T cell lymphomas (AITL). The diagnostic value of these mutations is now being investigated. Circulating tumor DNAs (ctDNAs) may offer a non-invasive testing for diagnosis and disease monitoring of cancers. To investigate whether these mutations are useful markers for ctDNAs in AITL and its related lymphomas, we performed targeted sequencing for TET2, RHOA, DNMT3A, and IDH2 in paired tumors and cell-free DNAs from 14 patients at diagnosis...
June 20, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28634182/sf3b1-initiating-mutations-in-mds-with-ring-sideroblasts-target-lymphomyeloid-hematopoietic-stem-cells
#2
Teresa Mortera-Blanco, Marios Dimitriou, Petter S Woll, Mohsen Karimi, Edda Elvarsdottir, Simona Conte, Magnus Tobiasson, Monika Jansson, Iyadh Douagi, Matahi Moarii, Leonie Saft, Elli Papaemmanuil, Sten Eirik W Jacobsen, Eva Hellström-Lindberg
Mutations in the RNA splicing gene SF3B1 are found in more than 80% of patients with myelodysplastic syndrome with ring sideroblasts (MDS-RS). We investigated the origin of SF3B1 mutations within the bone marrow hematopoietic stem and progenitor cell compartments in patients with MDS-RS. Screening for recurrently mutated genes in the mononuclear cell fraction revealed mutations in SF3B1 in 39 of 40 cases (97.5%), combined with TET2 and DNMT3A in 11 (28%) and 6 (15%) patients, respectively. All recurrent mutations identified in mononuclear cells could be tracked back to the phenotypically defined hematopoietic stem cell (HSC) compartment in all investigated patients, and were also present in downstream myeloid and erythroid progenitor cells...
June 20, 2017: Blood
https://www.readbyqxmd.com/read/28629431/microrna-330-3p-promotes-cell-invasion-and-metastasis-in-non-small-cell-lung-cancer-through-gria3-by-activating-mapk-erk-signaling-pathway
#3
Chun-Hua Wei, Gang Wu, Qian Cai, Xi-Can Gao, Fan Tong, Rui Zhou, Rui-Guang Zhang, Ji-Hua Dong, Yu Hu, Xiao-Rong Dong
BACKGROUND: Brain metastasis (BM) is associated with poor prognosis in patients with non-small cell lung cancer (NSCLC). Recent studies demonstrated that microRNA-330-3p (miR-330-3p) was involved in NSCLC brain metastasis (BM). However, the exact parts played by miR-330-3p in BM of NSCLC remain unknown. Discovery and development of biomarkers and elucidation of the mechanism underlying BM in NSCLC is critical for effective prophylactic interventions. Here, we evaluated the expression and biological effects of miR-330-3p in NSCLC cells and explored the underlying mechanism of miR-330-3p in promoting cell migration and invasion in NSCLC...
June 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28619512/part-1-functions-as-a-competitive-endogenous-rna-for-promoting-tumor-progression-by-sponging-mir-143-in-colorectal-cancer
#4
Yongbo Hu, Zhen Ma, Yiming He, Wei Liu, Yu Su, Zongbin Tang
LncRNAs were altered in several cancers and played a crucial role in various biological activities and progressions of different diseases, including proliferation, chemical resistance, and metastasis. In the present study, we revealed that prostrate androgen-regulated transcript-1 (PART-1) was highly expressed in colorectal cancer cells and tissues, and knockdown of PART-1 suppressed cell proliferation and metastasis, both in vitro and in vivo. In addition, PART-1 functioned as a ceRNA of DNMT3A, by sponging miR-143...
June 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28616699/flt3-itd-with-dnmt3a-r882-double-mutation-is-a-poor-prognostic-factor-in-chinese-patients-with-acute-myeloid-leukemia-after-chemotherapy-or-allogeneic-hematopoietic-stem-cell-transplantation
#5
Shanhao Tang, Hongjie Shen, Xinliang Mao, Haiping Dai, Xiaming Zhu, Shengli Xue, Zixuan Ding, Jing Lu, Depei Wu, Xiaowen Tang
To investigate clinical characteristics and outcomes of transplantation in AML patients with FLT3-ITD/DNMT3A double mutation, we retrospectively analyzed 206 Chinese patients with AML after Sanger sequencing. Our analysis showed that AML patients with FLT3-ITD and DNMT3A R882 mutations had a higher white blood cell count and a lower complete remission (CR) rate after first induction chemotherapy. All 206 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in status of CR. These results indicate that AML patients with FLT3-ITD and DNMT3A R882 double mutation show a higher 2-year cumulative incidence of relapse (CIR), lower 2-year overall survival (OS) rate, and lower 2-year leukocyte-free survival (LFS) after allo-HSCT...
June 14, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28616099/epigenetic-silencing-of-sall3-is-an-independent-predictor-of-poor-survival-in-head-and-neck-cancer
#6
Kiyoshi Misawa, Daiki Mochizuki, Atsushi Imai, Yuki Misawa, Shiori Endo, Masato Mima, Hideya Kawasaki, Thomas E Carey, Takeharu Kanazawa
BACKGROUND: This study examined Sal-like protein (SALL)3 methylation profiles of head and neck cancer (HNSCC) patients at diagnosis and follow-up and evaluated their prognostic significance and value as a biomarker. SALL3 expression was examined in a panel of cell lines by quantitative reverse transcription polymerase chain reaction (RT-PCR). The methylation status of the SALL3 promoter was examined by quantitative methylation-specific PCR. RESULTS: SALL3 promoter methylation was associated with transcriptional inhibition and was correlated with disease recurrence in 64...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28614801/dna-methyltransferase-3b-regulates-articular-cartilage-homeostasis-by-altering-metabolism
#7
Jie Shen, Cuicui Wang, Daofeng Li, Taotao Xu, Jason Myers, John M Ashton, Ting Wang, Michael J Zuscik, Audrey McAlinden, Regis J O'Keefe
Osteoarthritis (OA) is the most common form of arthritis worldwide. It is a complex disease affecting the whole joint but is generally characterized by progressive degradation of articular cartilage. Recent genome-wide association screens have implicated distinct DNA methylation signatures in OA patients. We show that the de novo DNA methyltransferase (Dnmt) 3b, but not Dnmt3a, is present in healthy murine and human articular chondrocytes and its expression decreases in OA mouse models and in chondrocytes from human OA patients...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28614798/dnmt3a-mediated-inhibition-of-wnt-in-cardiac-progenitor-cells-improves-differentiation-and-remote-remodeling-after-infarction
#8
Aurelia De Pauw, Emilie Andre, Belaid Sekkali, Caroline Bouzin, Hrag Esfahani, Nicolas Barbier, Axelle Loriot, Charles De Smet, Laetitia Vanhoutte, Stéphane Moniotte, Bernhard Gerber, Vittoria di Mauro, Daniele Catalucci, Olivier Feron, Denise Hilfiker-Kleiner, Jean-Luc Balligand
Adult cardiac progenitor cells (CPCs) display a low capacity to differentiate into cardiomyocytes in injured hearts, strongly limiting the regenerative capacity of the mammalian myocardium. To identify new mechanisms regulating CPC differentiation, we used primary and clonally expanded Sca-1+ CPCs from murine adult hearts in homotypic culture or coculture with cardiomyocytes. Expression kinetics analysis during homotypic culture differentiation showed downregulation of Wnt target genes concomitant with increased expression of the Wnt antagonist, Wnt inhibitory factor 1 (Wif1), which is necessary to stimulate CPC differentiation...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28614398/5-aza-2-deoxycytidine-in-the-medial-prefrontal-cortex-regulates-alcohol-related-behavior-and-ntf3-trkc-expression-in-rats
#9
Xiaomeng Qiao, Fangyuan Yin, Yuanyuan Ji, Yunxiao Li, Peng Yan, Jianghua Lai
Recent studies have indicated that DNA methylation plays an important role in the development of alcohol abuse. 5-Aza-2'-deoxycytidine (5-Aza-dc), an inhibitor of DNA methyltransferases, was FDA approved for myelodysplastic syndrome treatment. However, it is unclear whether 5-Aza-dc is involved in alcohol abuse. In this study, using a chronic alcohol exposure model in rats, 5-Aza-dc was injected into the medial prefrontal cortex (mPFC). Alcohol-drinking behavior and the anxiety related behavior were evaluated by two-bottle choice and open field test...
2017: PloS One
https://www.readbyqxmd.com/read/28607180/p53-is-essential-for-dna-methylation-homeostasis-in-na%C3%A3-ve-embryonic-stem-cells-and-its-loss-promotes-clonal-heterogeneity
#10
Ayala Tovy, Adam Spiro, Ryan McCarthy, Zohar Shipony, Yael Aylon, Kendra Alton, Elena Ainbinder, Noa Furth, Amos Tanay, Michelle Barton, Moshe Oren
DNA methylation is a key regulator of embryonic stem cell (ESC) biology, dynamically changing between naïve, primed, and differentiated states. The p53 tumor suppressor is a pivotal guardian of genomic stability, but its contributions to epigenetic regulation and stem cell biology are less explored. We report that, in naïve mouse ESCs (mESCs), p53 restricts the expression of the de novo DNA methyltransferases Dnmt3a and Dnmt3b while up-regulating Tet1 and Tet2, which promote DNA demethylation. The DNA methylation imbalance in p53-deficient (p53(-/-)) mESCs is the result of augmented overall DNA methylation as well as increased methylation landscape heterogeneity...
June 12, 2017: Genes & Development
https://www.readbyqxmd.com/read/28597690/dna-methylation-and-copy-number-variation-analyses-of-human-embryonic-stem-cell-derived-neuroprogenitors-after-low-dose-decabromodiphenyl-ether-and-or-bisphenol-a-exposure
#11
L Du, W Sun, X M Li, X Y Li, W Liu, D Chen
The polybrominated diphenyl ether flame retardants decabromodiphenyl ether (BDE-209) and bisphenol A (BPA) are environmental contaminants that can cross the placenta and exert toxicity in the developing fetal nervous system. Copy number variants (CNVs) play a role in a number of genetic disorders and may be implicated in BDE-209/BPA teratogenicity. In this study, we found that BDE-209 and/or BPA exposure decreased neural differentiation efficiency of human embryonic stem cells (hESCs), although there was a >90% induction of neuronal progenitor cells (NPCs) from exposed hESCs...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28597341/in-silico-prediction-and-validation-of-gfap-as-an-mir-3099-target-in-mouse-brain
#12
Shahidee Zainal Abidin, Jia-Wen Leong, Marzieh Mahmoudi, Norshariza Nordin, Syahril Abdullah, Pike-See Cheah, King-Hwa Ling
MicroRNAs are small non-coding RNAs that play crucial roles in the regulation of gene expression and protein synthesis during brain development. MiR-3099 is highly expressed throughout embryogenesis, especially in the developing central nervous system. Moreover, miR-3099 is also expressed at a higher level in differentiating neurons in vitro, suggesting that it is a potential regulator during neuronal cell development. This study aimed to predict the target genes of miR-3099 via in-silico analysis using four independent prediction algorithms (miRDB, miRanda, TargetScan, and DIANA-micro-T-CDS) with emphasis on target genes related to brain development and function...
June 8, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28596252/success-in-bone-marrow-failure-novel-therapeutic-directions-based-on-the-immune-environment-of-myelodysplastic-syndromes
#13
REVIEW
Alyssa H Cull, Michael J Rauh
Myelodysplastic syndromes (MDS) are clonal neoplasms of aging that are associated with BM failure, related cytopenias, fatigue, susceptibility to infections, bruising, bleeding, a shortened lifespan, and a propensity for leukemic transformation. Most frail, elderly patients are not candidates for curative allogeneic BM transplantations and instead receive expectant management, supportive blood transfusions, or empirical, nontargeted therapy. It has been known for some time that MDS arises in an abnormal BM immune environment; however, connections have only recently been established with recurring MDS-associated mutations...
June 8, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28587163/a-tox21-approach-to-altered-epigenetic-landscapes-assessing-epigenetic-toxicity-pathways-leading-to-altered-gene-expression-and-oncogenic-transformation-in-vitro
#14
REVIEW
Craig L Parfett, Daniel Desaulniers
An emerging vision for toxicity testing in the 21st century foresees in vitro assays assuming the leading role in testing for chemical hazards, including testing for carcinogenicity. Toxicity will be determined by monitoring key steps in functionally validated molecular pathways, using tests designed to reveal chemically-induced perturbations that lead to adverse phenotypic endpoints in cultured human cells. Risk assessments would subsequently be derived from the causal in vitro endpoints and concentration vs...
June 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28583846/epigenetic-effects-of-inhibition-of-heat-shock-protein-90-hsp90-in-human-pancreatic-and-colon-cancer
#15
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/28581528/dna-methylation-variations-are-required-for-epithelial-to-mesenchymal-transition-induced-by-cancer-associated-fibroblasts-in-prostate-cancer-cells
#16
C Pistore, E Giannoni, T Colangelo, F Rizzo, E Magnani, L Muccillo, G Giurato, M Mancini, S Rizzo, M Riccardi, N Sahnane, V Del Vescovo, K Kishore, M Mandruzzato, F Macchi, M Pelizzola, M A Denti, D Furlan, A Weisz, V Colantuoni, P Chiarugi, I M Bonapace
Widespread genome hypo-methylation and promoter hyper-methylation of epithelium-specific genes are hallmarks of stable epithelial-to-mesenchymal transition (EMT), which in prostate cancer (PCa) correlates with castration resistance, cancer stem cells generation, chemoresistance and worst prognosis. Exploiting our consolidated 'ex-vivo' system, we show that cancer-associated fibroblasts (CAFs) released factors have pivotal roles in inducing genome methylation changes required for EMT and stemness in EMT-prone PCa cells...
June 5, 2017: Oncogene
https://www.readbyqxmd.com/read/28578488/17%C3%AE-estradiol-increases-non-cpg-methylation-in-exon-1-of-the-rainbow-trout-oncorhynchus-mykiss-myod-gene
#17
Prasanthi P Koganti, Jian Wang, Beth Cleveland, Jianbo Yao
MyoD is an important myogenic transcription factor necessary for the differentiation of myogenic precursor cells (MPC) to form mature myotubes, a process essential for muscle growth. Epigenetic markers such as CpH methylation are known gene regulators that are important for the differentiation process. In this study, we investigated whether DNA methylation is a potential mechanism associated with the ability of 17β-estradiol (E2) to reduce MyoD gene expression and muscle growth in rainbow trout. Rainbow trout received a single intraperitoneal injection of E2 or the injection vehicle (control)...
June 3, 2017: Marine Biotechnology
https://www.readbyqxmd.com/read/28574380/mthfr-gene-c677t-polymorphism-and-levels-of-dna-methyltrasferases-in-subclinical-hypothyroidism
#18
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
#19
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/28555413/epigenetic-dysregulation-of-hematopoietic-stem-cells-and-preleukemic-state
#20
REVIEW
Hiroyoshi Kunimoto, Hideaki Nakajima
Recent genetic analyses have revealed that premalignant somatic mutations in hematopoietic cells are common in older people without an evidence of hematologic malignancies, leading to clonal hematopoietic expansion. This phenomenon has been termed clonal hematopoiesis of indeterminate potential (CHIP). Frequency of such clonal somatic mutations increases with age: in 5-10% of people older than 70 years and around 20% of people older than 90 years. The most commonly mutated genes found in individuals with CHIP were epigenetic regulators, including DNA methyltransferase 3A (DNMT3A), Ten-eleven-translocation 2 (TET2), and Additional sex combs-like 1 (ASXL1), which are also recurrently mutated in myeloid malignancies...
July 2017: International Journal of Hematology
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