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https://www.readbyqxmd.com/read/28522693/histone-h3-3k27m-represses-p16-to-accelerate-gliomagenesis-in-a-murine-model-of-dipg
#1
Francisco J Cordero, Zhiqing Huang, Carole Grenier, Xingyao He, Guo Hu, Roger E McLendon, Susan K Murphy, Rintaro Hashizume, Oren J Becher
Diffuse Intrinsic Pontine Glioma (DIPG) is a highly aggressive pediatric brainstem tumor genetically distinguished from adult GBM by the high prevalence of the K27M mutation in the histone H3 variant H3.3 (H3F3A). This mutation reprograms the H3K27me3 epigenetic landscape of DIPG by inhibiting the H3K27-specific histone methyltransferase EZH2. This globally reduces H3K27me2/3, critical repressive marks responsible for cell fate decisions, and also causes focal gain of H3K27me3 throughout the epigenome. To date the tumor-driving effects of H3...
May 18, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28515962/analyses-of-publicly-available-genomics-resources-define-fgf-2-expressing-bladder-carcinomas-as-emt-prone-proliferative-tumors-with-low-mutation-rates-and-high-expression-of-ctla-4-pd-1-and-pd-l1
#2
Elizabeth A McNiel, Philip N Tsichlis
FGF-2 is overexpressed in a subset of invasive bladder carcinomas and its overexpression correlates with poor prognosis. Analyses of publicly available databases addressing the molecular mechanisms that may be responsible for the poor prognosis of these tumors, revealed that FGF-2 expression correlates positively with the expression of EMT-promoting transcription factors and with changes in gene expression that are characteristic of EMT. The same analyses also revealed that FGF-2 correlates negatively with the expression, mutation and copy number variations of FGFR-3, all of which are associated with non-invasive bladder carcinomas...
2017: Signal Transduction and Targeted Therapy
https://www.readbyqxmd.com/read/28513825/loss-of-tet1-facilitates-dld1-colon-cancer-cell-migration-via-h3k27me3-mediated-down-regulation-of-e-cadherin
#3
Zhen Zhou, Hong-Sheng Zhang, Yang Liu, Zhong-Guo Zhang, Guang-Yuan Du, Hu Li, Xiao-Ying Yu, Ying-Hui Huang
Epigenetic modifications such as histone modifications and cytosine hydroxymethylation are linked to tumorigenesis. Loss of 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation 1 (TET1) down-regulation facilitates tumor initiation and development. However, the mechanisms by which loss of TET1 knockdown promotes malignancy development remains unclear. Here, we report that TET1 knockdown induced epithelial-mesenchymal transition (EMT) and increased cancer cell growth, migration and invasion in DLD1 cells...
May 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28512107/divergent-requirements-for-ezh1-in-heart-development-versus-regeneration
#4
Shanshan Ai, Xianhong Yu, Yumei Li, Yong Peng, Chen Li, Yanzhu Yue, Ge Tao, Chuan-Yun Li, William T Pu, Aibin He
Rationale: Polycomb repressive complex 2 (PRC2) is a major epigenetic repressor that deposits methylation on histone H3 on lysine 27 (H3K27me) and controls differentiation and function of many cells, including cardiac myocytes. EZH1 and EZH2 are two alternative catalytic subunits with partial functional redundancy. The relative roles of EZH1 and EZH2 in heart development and regeneration are unknown. Objective: We compared the roles of EZH1 versus EZH2 in heart development and neonatal heart regeneration. Methods and Results: Heart development was normal in Ezh1(-/-) (E1KO) and Ezh2(f/f)::cTNT(-Cre) (E2KO) embryos...
May 16, 2017: Circulation Research
https://www.readbyqxmd.com/read/28506684/study-of-preanalytic-and-analytic-variables-for-clinical-next-generation-sequencing-of-circulating-cell-free-nucleic-acid
#5
Meenakshi Mehrotra, Rajesh R Singh, Wei Chen, Richard S P Huang, Alaa A Almohammedsalim, Bedia A Barkoh, Crystal M Simien, Marcos Hernandez, Carmen Behrens, Keyur P Patel, Mark J Routbort, Russell R Broaddus, L Jeffrey Medeiros, Ignacio I Wistuba, Scott Kopetz, Rajyalakshmi Luthra
Detection of mutations in plasma circulating cell-free DNA (cfDNA) by next-generation sequencing (NGS) has opened up new possibilities for monitoring treatment response and disease progression in patients with solid tumors. However, implementation of cfDNA genotyping in diagnostic laboratories requires systematic assessment of preanalytical parameters and analytical performance of NGS platforms. We assessed the effects of peripheral blood collection tube and plasma separation time on cfDNA yield and integrity and performance of the Ion PGM, Proton, and MiSeq NGS platforms...
May 12, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28500253/linc00341-exerts-an-anti-inflammatory-effect-on-endothelial-cells-by-repressing-vcam1
#6
Tse-Shun Huang, Kuei-Chun Wang, Sara Quon, Phu Nguyen, Ting-Yu Chang, Zhen Chen, Yi-Shuan Li, Shankar Subramaniam, John Y-J Shyy, Shu Chien
The long non-coding RNAs (lncRNAs), which constitute a large portion of the transcriptome, have gained intense research interest because of their roles in regulating physiological and pathophysiological functions in the cell. We identified from RNA-seq profiling a set of lncRNAs in cultured human umbilical vein endothelial cells (HUVECs) that are differentially regulated by atheroprotective vs. atheroprone shear flows. Among the comprehensively annotated lncRNAs, including both known and novel transcripts, LINC00341 is one of the most abundant lncRNAs in endothelial cells...
May 12, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28490575/ezh2-regulates-the-developmental-timing-of-effectors-of-the-pre-antigen-receptor-checkpoints
#7
Jennifer A Jacobsen, Jennifer Woodard, Malay Mandal, Marcus R Clark, Elizabeth T Bartom, Mikael Sigvardsson, Barbara L Kee
The histone methyltransferase EZH2 is required for B and T cell development; however, the molecular mechanisms underlying this requirement remain elusive. In a murine model of lymphoid-specific EZH2 deficiency we found that EZH2 was required for proper development of adaptive, but not innate, lymphoid cells. In adaptive lymphoid cells EZH2 prevented the premature expression of Cdkn2a and the consequent stabilization of p53, an effector of the pre-Ag receptor checkpoints. Deletion of Cdkn2a in EZH2-deficient lymphocytes prevented p53 stabilization, extended lymphocyte survival, and restored differentiation resulting in the generation of mature B and T lymphocytes...
May 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28490465/dual-inhibition-of-ezh2-and-ezh1-sensitizes-prc2-dependent-tumors-to-proteasome-inhibition
#8
Ola Rizq, Naoya Mimura, Motohiko Oshima, Atsunori Saraya, Shuhei Koide, Yuko Kato, Kazumasa Aoyama, Yaeko Nakajima-Takagi, Changshan Wang, Tetsuhiro Chiba, Anqi Ma, Jian Jin, Tohru Iseki, Chiaki Nakaseko, Atsushi Iwama
<br /> <p>EZH2 and EZH1, the catalytic components of polycomb repressive complex 2 (PRC2), trigger trimethylation of H3K27 (H3K27me3) to repress the transcription of target genes and are implicated in the pathogenesis of various cancers including multiple myeloma (MM) and prostate cancer. Here, we investigated the preclinical effects of UNC1999, a dual inhibitor of EZH2 and EZH1, in combination with proteasome inhibitors on MM and prostate cancer.</p> <br /><br />Experimental Design: <br /> <p>In vitro and in vivo efficacy of UNC1999 and the combination with proteasome inhibitors was evaluated in MM cell lines, primary patient cells and in a xenograft model...
May 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28487787/ebv-negative-monomorphic-b-cell-posttransplant-lymphoproliferative-disorder-with-marked-morphologic-pleomorphism-and-pathogenic-mutations-in-asxl1-bcor-cdkn2a-nf1-and-tp53
#9
Agata M Bogusz
Posttransplant lymphoproliferative disorders (PTLDs) are a diverse group of lymphoid or plasmacytic proliferations frequently driven by Epstein-Barr virus (EBV). EBV-negative PTLDs appear to represent a distinct entity. This report describes an unusual case of a 33-year-old woman that developed a monomorphic EBV-negative PTLD consistent with diffuse large B-cell lymphoma (DLBCL) 13 years after heart-lung transplant. Histological examination revealed marked pleomorphism of the malignant cells including nodular areas reminiscent of classical Hodgkin lymphoma (cHL) with abundant large, bizarre Hodgkin-like cells...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28485572/citrullination-methylation-crosstalk-on-histone-h3-regulates-er-target-gene-transcription
#10
Kathleen W Clancy, Anna-Maria Russell, Venkataraman Subramanian, Hannah Nguyen, Yuewei Qian, Robert M Campbell, Paul R Thompson
Posttranslational modifications of histone tails are a key contributor to epigenetic regulation. Histone H3 Arg26 and Lys27 are both modified by multiple enzymes, and their modifications have profound effects on gene expression. Citrullination of H3R26 by PAD2 and methylation of H3K27 by PRC2 have opposing downstream impacts on gene regulation; H3R26 citrullination activates gene expression, and H3K27 methylation represses gene expression. Both of these modifications are drivers of a variety of cancers, and their writer enzymes, PAD2 and EZH2, are the targets of drug therapies...
May 9, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28484169/current-diagnosis-and-treatment-for-myelodysplastc-syndromes
#11
Tomoko Hata
Genetic analysis of myelodysplastic syndrome (MDS) using next-generation sequencing yields medcially important information, showing gene mutations in 90% of MDS cases. The World Health Organization (WHO) classification was revised in 2016 to incorporate SF3B1 gene mutations, frequently seen in MDS with ringed sideroblasts, into the diagnostic criteria. Unlike the poor prognosis seen in cases with ASXL1, EZH2, RUNX1 and in particular, TP53 MDS-related mutations, SF3B1 gene mutations show a favorable prognosis...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28476883/the-long-non-coding-rna-hotair-enhances-pancreatic-cancer-resistance-to-tnf-related-apoptosis-inducing-ligand
#12
Shan-Zhong Yang, Fei Xu, Tong Zhou, Xinyang Zhao, Jay M McDonald, Yabing Chen
Pancreatic cancer is a malignant neoplasm with a high mortality rate. Therapeutic agents that activate TNF-related apoptosis inducing ligand (TRAIL)-induced apoptosis have shown promising efficacy, but many pancreatic cancers are resistant to TRAIL therapy. Epigenetic regulation plays important roles in tumor pathogenesis and resistance, and a recent study indicated that the long non-coding RNA HOX transcript antisense RNA (HOTAIR) is overexpressed in pancreatic cancer. However, the role of HOTAIR in pancreatic cancer resistance to anticancer agents is unknown...
May 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28475857/mutations-in-epigenetic-regulation-genes-are-a-major-cause-of-overgrowth-with-intellectual-disability
#13
Katrina Tatton-Brown, Chey Loveday, Shawn Yost, Matthew Clarke, Emma Ramsay, Anna Zachariou, Anna Elliott, Harriet Wylie, Anna Ardissone, Olaf Rittinger, Fiona Stewart, I Karen Temple, Trevor Cole, Shazia Mahamdallie, Sheila Seal, Elise Ruark, Nazneen Rahman
To explore the genetic architecture of human overgrowth syndromes and human growth control, we performed experimental and bioinformatic analyses of 710 individuals with overgrowth (height and/or head circumference ≥+2 SD) and intellectual disability (OGID). We identified a causal mutation in 1 of 14 genes in 50% (353/710). This includes HIST1H1E, encoding histone H1.4, which has not been associated with a developmental disorder previously. The pathogenic HIST1H1E mutations are predicted to result in a product that is less effective in neutralizing negatively charged linker DNA because it has a reduced net charge, and in DNA binding and protein-protein interactions because key residues are truncated...
May 4, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28469799/histone-h3k14-hypoacetylation-and-h3k27-hypermethylation-along-with-hdac1-up-regulation-and-kdm6b-down-regulation-are-associated-with-active-pulmonary-tuberculosis-disease
#14
Yung-Che Chen, Tung-Ying Chao, Sum-Yee Leung, Chung-Jen Chen, Chao-Chien Wu, Wen-Feng Fang, Yi-Hsi Wang, Huang-Chih Chang, Ting-Ya Wang, Yong-Yong Lin, Yi-Xin Zheng, Meng-Chih Lin, Chang-Chun Hsiao
The aim of this study is to determine the roles of global histone acetylation (Ac)/methylation (me), their modifying enzymes, and gene-specific histone enrichment in active pulmonary tuberculosis (TB) disease. Global histone H3K27me3, H3K27me2, H3K9me3, H3K9Ac, and H3K14Ac expressions, and their modifying enzyme expressions, including KDM1A, KDM6B, EZH2, HDAC1, and HDAC2, were assessed in blood leukocytes from 81 patients with active pulmonary TB disease and 44 matched healthy subjects (HS). TLR2, TNF-α, IFN-γ, and IL12B-specific histone enrichment of peripheral blood mononuclear cells was measured by chromatin immunoprecipitation method...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28461508/conditional-knockin-of-dnmt3a-r878h-initiates-acute-myeloid-leukemia-with-mtor-pathway-involvement
#15
Yu-Jun Dai, Yue-Ying Wang, Jin-Yan Huang, Li Xia, Xiao-Dong Shi, Jie Xu, Jing Lu, Xian-Bin Su, Ying Yang, Wei-Na Zhang, Pan-Pan Wang, Song-Fang Wu, Ting Huang, Jian-Qing Mi, Ze-Guang Han, Zhu Chen, Sai-Juan Chen
DNMT3A is frequently mutated in acute myeloid leukemia (AML). To explore the features of human AML with the hotspot DNMT3A R882H mutation, we generated Dnmt3a R878H conditional knockin mice, which developed AML with enlarged Lin(-)Sca1(+)cKit(+) cell compartments. The transcriptome and DNA methylation profiling of bulk leukemic cells and the single-cell RNA sequencing of leukemic stem/progenitor cells revealed significant changes in gene expression and epigenetic regulatory patterns that cause differentiation arrest and growth advantage...
May 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28454437/polycomb-group-expression-signatures-in-the-malignant-progression-of-gliomas
#16
Qi Hu, Weining Wu, Ailiang Zeng, Tianfu Yu, Feng Shen, Er Nie, Yingyi Wang, Ning Liu, Junxia Zhang, Yongping You
Polycomb group (PcG) proteins form at least two key complexes, namely polycomb repressive complex 1 and polycomb repressive complex 2. These complexes are involved in the progression of various cancers. Systematic research has not been conducted on the aberrant expression of PcG members in gliomas. Using the Chinese Glioma Genome Atlas data set, PcG expression patterns between normal brain tissues and glioma samples were analyzed, and a PcG-based classifier was then developed using BRB Cox regression and risk-score model...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28447382/quantitative-proteomic-analysis-of-ezh2-inhibition-in-acute-myeloid-leukemia-reveals-the-targets-and-pathways-that-precede-the-induction-of-cell-death
#17
Jarrod J Sandow, Giuseppe Infusini, Aliaksei Z Holik, Gabriela Brumatti, Tessa V Averink, Paul G Ekert, Andrew I Webb
PURPOSE: Chromosomal translocation of the Mixed Lineage Leukemia (MLL) locus generates fusion proteins that drive acute myeloid leukemia (AML) resulting in atypical histone methyltransferase activity and alterations in the epigenetic regulation of gene expression. Targeting histone regulators, such as Enhancer of Zeste Homologue 2 (EZH2), has shown promise in AML. Profiling differential protein expression following inhibition of epigenetic regulators in AML may help to identify novel targets for therapeutics...
April 26, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28445937/methylation-mediated-silencing-of-microrna-211-promotes-cell-growth-and-epithelial-to-mesenchymal-transition-through-activation-of-the-akt-%C3%AE-catenin-pathway-in-gbm
#18
Weidong Li, Xiaobo Miao, Lingling Liu, Yue Zhang, Xuejun Jin, Xiaojun Luo, Hai Gao, Xubin Deng
Aberrant expression of miR-211 has frequently been reported in cancer studies; however, its role in glioblastoma multiforme (GBM) has not been examined in detail. We investigated the function and the underlying mechanism of miR-211 in GBM. We revealed that miR-211 was downregulated in GBM tissues and cell lines. Restoration of miR-211 inhibited GBM cell growth and invasion both in vitro and in vivo. The epithelial to mesenchymal transition (EMT) phenotype was reversed when miR-211 expression was restored. HMGA2 was identified as a down-stream target of miR-211...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445158/the-hdac-inhibitor-valproate-induces-a-bivalent-status-of-the-cd20-promoter-in-cll-patients-suggesting-distinct-epigenetic-regulation-of-cd20-expression-in-cll-in-vivo
#19
Annarita Scialdone, Muhammad Sharif Hasni, Jesper Kofoed Damm, Andreas Lennartsson, Urban Gullberg, Kristina Drott
Treatment with anti-CD20 antibodies is only moderately efficient in chronic lymphocytic leukemia (CLL), a feature which has been explained by the inherently low CD20 expression in CLL. It has been shown that CD20 is epigenetically regulated and that histone deacetylase inhibitors (HDACis) can increase CD20 expression in vitro in CLL. To assess whether HDACis can upregulate CD20 also in vivo in CLL, the HDACi valproate was given to three del13q/NOTCH1wt CLL patients and CD20 levels were analysed (the PREVAIL study)...
April 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444909/the-histone-methyltransferase-ezh2-is-a-therapeutic-target-in-small-cell-carcinoma-of-the-ovary-hypercalcemic-type
#20
Yemin Wang, Shary Yuting Chen, Anthony N Karnezis, Shane Colborne, Nancy Dos Santos, Jessica D Lang, William P D Hendricks, Krystal A Orlando, Damian Yap, Friedrich Kommoss, Marcel B Bally, Gregg B Morin, Jeffrey M Trent, Bernard E Weissman, David G Huntsman
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but aggressive and untreatable malignancy affecting young women. We and others recently discovered that SMARCA4, a gene encoding the ATPase of the SWI/SNF chromatin-remodeling complex, is the only gene recurrently mutated in the majority of SCCOHT. The low somatic complexity of SCCOHT genomes and the prominent role of the SWI/SNF chromatin-remodeling complex in transcriptional control of genes suggest that SCCOHT cells may rely on epigenetic rewiring for oncogenic transformation...
April 26, 2017: Journal of Pathology
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