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HDAC1 HDAC2

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https://www.readbyqxmd.com/read/27903278/an-overview-on-the-role-of-dietary-phenolics-for-the-treatment-of-cancers
#1
REVIEW
Preethi G Anantharaju, Prathima C Gowda, Manjunatha G Vimalambike, SubbaRao V Madhunapantula
Plant derived phenolic compounds have been shown to inhibit the initiation and progression of cancers by modulating genes regulating key processes such as: (a) oncogenic transformation of normal cells; (b) growth and development of tumors; and (c) angiogenesis and metastasis. Recent studies focusing on identifying the molecular basis of plant phenolics-induced cancer cell death have demonstrated down-regulation of: (a) oncogenic survival kinases such as PI3K and Akt; (b) cell proliferation regulators that include Erk1/2, D-type Cyclins, and Cyclin Dependent Kinases (CDKs); (c) transcription factors such as NF-kβ, NRF2 and STATs; (d) histone deacetylases HDAC1 and HDAC2; and (e) angiogenic factors VEGF, FGFR1 and MIC-1...
December 1, 2016: Nutrition Journal
https://www.readbyqxmd.com/read/27886239/histone-deacetylase-1-plays-a-predominant-pro-oncogenic-role-in-e%C3%AE-myc-driven-b-cell-lymphoma
#2
Vincent Pillonel, Nina Reichert, Chun Cao, Marinus R Heideman, Teppei Yamaguchi, Gabriele Matthias, Alexandar Tzankov, Patrick Matthias
The two histone deacetylases (Hdacs), Hdac1 and Hdac2, are erasers of acetylation marks on histone tails, and are important regulators of gene expression that were shown to play important roles in hematological malignancies. However, several recent studies reported opposing tumor-suppressive or tumor-promoting roles for Hdac1 and Hdac2. Here, we investigated the functional role of Hdac1 and Hdac2 using the Eμ-myc mouse model of B cell lymphoma. We demonstrate that Hdac1 and Hdac2 have a pro-oncogenic role in both Eμ-myc tumorigenesis and tumor maintenance...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27868267/reduced-microrna-188-3p-expression-contributes-to-apoptosis-of-spermatogenic-cells-in-patients-with-azoospermia
#3
Wen-Yan Song, Hui Meng, Xue-Gai Wang, Hai-Xia Jin, Gui-Dong Yao, Sen-Lin Shi, Liang Wu, Xiang-Yang Zhang, Ying-Pu Sun
BACKGROUND AND AIMS: Human mutL homologl (MLH1) works coordinately in sequential steps to initiate repair of DNA mismatches, and aberrant MLH1 expression is related to spermatogenetic malfunction. In the present study, MLH1 expression in patients with azoospermia was investigated, and moderating effects of miR-188-3p on MLH1 expression and spermatogenesis were identified. METHODS: Testicular tissues from 16 patients with obstructive azoospermia (OA) and non-obstructive azoospermia (NOA), and tissues of eight healthy patients were collected...
November 21, 2016: Cell Proliferation
https://www.readbyqxmd.com/read/27832326/silencing-of-histone-deacetylase-2-suppresses-malignancy-for-proliferation-migration-and-invasion-of-glioblastoma-cells-and-enhances-temozolomide-sensitivity
#4
Zhiqiang Zhang, Yunmin Wang, Jiehan Chen, Qijia Tan, Caijun Xie, Cong Li, Wengang Zhan, Mei Wang
Histone deacetylases (HDACs) can regulate the progression of various cancers, while their roles in glioblastoma multiforme (GBM) are not well known. Our present study investigated the expression of class I HDACs (HDAC1, 2, 3, 8) in GBM U87, A172, U251, and LN229 cells and compared their levels with that in primary normal human astrocytes (NHA) cells. It showed that HDAC2 expression is significantly up-regulated in GBM cells. Silencing of HDAC2 via its specific siRNAs can suppress the in vitro proliferation, migration, and invasion of GBM U87 and A172 cells...
November 10, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27818691/osteogenic-differentiation-of-human-amniotic-fluid-mesenchymal-stem-cells-is-determined-by-epigenetic-changes
#5
Monika Glemžaitė, Rūta Navakauskienė
Osteogenic differentiation of human amniotic fluid derived mesenchymal stem cells (AF-MSCs) has been widely studied in vitro and in vivo as a potential tool for regenerative medicine and tissue engineering. While most of the studies analyze changes in transcriptional profile during differentiation to date there is not much information regarding epigenetic changes in AF-MSCs during differentiation. The aim of our study was to evaluate epigenetic changes during osteogenic differentiation of AF-MS cells. Isolated AF-MSCs were characterized morphologically and osteogenic differentiation was confirmed by cell staining and determining expression of alkaline phosphatase and osteopontin by RT-qPCR...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27803663/environmental-enrichment-modified-epigenetic-mechanisms-in-samp8-mouse-hippocampus-by-reducing-oxidative-stress-and-inflammaging-and-achieving-neuroprotection
#6
Christian Griñan-Ferré, Dolors Puigoriol-Illamola, Verónica Palomera-Ávalos, David Pérez-Cáceres, Júlia Companys-Alemany, Antonio Camins, Daniel Ortuño-Sahagún, M Teresa Rodrigo, Mercè Pallàs
With the increase in life expectancy, aging and age-related cognitive impairments are becoming one of the most important issues for human health. At the same time, it has been shown that epigenetic mechanisms are emerging as universally important factors in life expectancy. The Senescence Accelerated Mouse P8 (SAMP8) strain exhibits age-related deterioration evidenced in learning and memory abilities and is a useful model of neurodegenerative disease. In SAMP8, Environmental Enrichment (EE) increased DNA-methylation levels (5-mC) and reduced hydroxymethylation levels (5-hmC), as well as increased histone H3 and H4 acetylation levels...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27781405/valproic-acid-enhances-the-neural-differentiation-of-human-placenta-derived-mesenchymal-stem-cells-in-vitro
#7
Manasi Talwadekar, Sophia Fernandes, Vaijayanti Kale, Lalita Limaye
Mesenchymal stem cells (MSCs) are known to express a wide range of markers belonging to all the three lineages: mesodermal, ectodermal and endodermal. Therefore, the possibility of their transdifferentiation towards a neural lineage has been an aspect of active research. In the present study, MSCs were isolated from human placental tissue (P-MSC) and subjected them to neural differentiation. It was found that the P-MSCs differentiated towards neural lineage in appropriate differentiation conditions. However, when a histone deacetylase (HDAC) inhibitor - valproic acid (VPA) - was incorporated in the medium, there was a further increase in their neural differentiation potential...
October 25, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27761828/modulation-of-stat1-driven-transcriptional-activity-by-histone-deacetylases
#8
Benjamin Y Owusu, Lidija Klampfer
The luciferase (LUC) reporter assay is commonly used to study gene expression at the transcriptional level. It is convenient, fast, sensitive, inexpensive, and provides quantitative data about small changes in transcription. Signal transducer and activator of transcription 1 (STAT1) is a transcription factor that plays a crucial role in signaling by interferons (IFNs). Here, we describe LUC reporter studies that address the role of histone deacetylase (HDAC) activity in STAT1-dependent gene activation. These experiments include overexpression of HDAC1, HDAC2, HDAC3, and HDAC4 as well as silencing of HDAC1, HDAC2, and HDAC3 through RNA interference in mammalian cancer cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27729849/hdac3-but-not-hdac2-mediates-visual-experience-dependent-radial-glia-proliferation-in-the-developing-xenopus-tectum
#9
Juanmei Gao, Hangze Ruan, Xianjie Qi, Yi Tao, Xia Guo, Wanhua Shen
Radial glial cells (RGs) are one of the important progenitor cells that can differentiate into neurons or glia to form functional neural circuits in the developing central nervous system (CNS). Histone deacetylases (HDACs) has been associated with visual activity dependent changes in BrdU-positive progenitor cells in the developing brain. We previously have shown that HDAC1 is involved in the experience-dependent proliferation of RGs. However, it is less clear whether two other members of class I HDACs, HDAC2 and HDAC3, are involved in the regulation of radial glia proliferation...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27721407/hdac1-and-hdac2-integrate-the-expression-of-p53-mutants-in-pancreatic-cancer
#10
N Stojanovic, Z Hassan, M Wirth, P Wenzel, M Beyer, C Schäfer, P Brand, A Kroemer, R H Stauber, R M Schmid, A Arlt, A Sellmer, S Mahboobi, R Rad, M Reichert, D Saur, O H Krämer, G Schneider
Mutation of p53 is a frequent genetic lesion in pancreatic cancer being an unmet clinical challenge. Mutants of p53 have lost the tumour-suppressive functions of wild type p53. In addition, p53 mutants exert tumour-promoting functions, qualifying them as important therapeutic targets. Here, we show that the class I histone deacetylases HDAC1 and HDAC2 contribute to maintain the expression of p53 mutants in human and genetically defined murine pancreatic cancer cells. Our data reveal that the inhibition of these HDACs with small molecule HDAC inhibitors (HDACi), as well as the specific genetic elimination of HDAC1 and HDAC2, reduce the expression of mutant p53 mRNA and protein levels...
October 10, 2016: Oncogene
https://www.readbyqxmd.com/read/27714131/c60-oh-22-a-potential-histone-deacetylase-inhibitor-with-anti-angiogenic-activity
#11
Chengdu Sun, Liming Wang, Dan Gao, Yuanming Pan, Yuliang Zhao, Chunying Chen, Mingzhou Guo
C60(OH)22 has been reported to suppress human cancer by inhibiting angiogenesis. However, its mechanism of action remains unclear. To explore the role and mechanism of C60(OH)22 in human pancreatic cancer, siRNA knockdown, immunofluorescence and a matrigel plug mouse model were employed. The results demonstrated that C60(OH)22 suppresses endothelial cell invasion and tube formation in vitro. C60(OH)22 suppresses angiogenesis in human umbilical vein endothelial cell (HUVEC) xenograft mice. The enzymatic activities of MMP2 and MMP9, as well as the expression levels of HDAC1, HDAC2, HIF-1α and VEGF, were inhibited by C60(OH)22...
September 15, 2016: Nanoscale
https://www.readbyqxmd.com/read/27672210/class-i-histone-deacetylase-hdac1-and-wrn-recq-helicase-contribute-additively-to-protect-replication-forks-upon-hydroxyurea-induced-arrest
#12
Keffy Kehrli, Michael Phelps, Pavlo Lazarchuk, Eleanor Chen, Ray Monnat, Julia M Sidorova
The WRN helicase/exonuclease is mutated in Werner syndrome of genomic instability and premature aging. WRN-depleted fibroblasts, although remaining largely viable, have a reduced capacity to maintain replication forks active during a transient hydroxyurea-induced arrest. A strand exchange protein, RAD51, is also required for replication fork maintenance, and here we show that recruitment of RAD51 to stalled forks is reduced in the absence of WRN. We performed a siRNA screen for genes that are required for viability of WRN-depleted cells after hydroxyurea treatment, and identified HDAC1, a member of the class I histone deacetylase family...
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27668390/mecp2-and-histone-deacetylases-1-and-2-in-dorsal-striatum-collectively-suppress-repetitive-behaviors
#13
Melissa Mahgoub, Megumi Adachi, Kanzo Suzuki, Xihui Liu, Ege T Kavalali, Maria H Chahrour, Lisa M Monteggia
Class I histone deacetylases (HDACs) Hdac1 and Hdac2 can associate together in protein complexes with transcriptional factors such as methyl-CpG-binding protein 2 (MeCP2). Given their high degree of sequence identity, we examined whether Hdac1 and Hdac2 were functionally redundant in mature mouse brain. We demonstrate that postnatal forebrain-specific deletion of both Hdac1 and Hdac2 in mice impacts neuronal survival and results in an excessive grooming phenotype caused by dysregulation of Sap90/Psd95-associated protein 3 (Sapap3; also known as Dlgap3) in striatum...
November 2016: Nature Neuroscience
https://www.readbyqxmd.com/read/27635950/connectivity-map-identifies-hdac-inhibition-as-a-treatment-option-of-high-risk-hepatoblastoma
#14
Alexander Beck, Corinna Eberherr, Michaela Hagemann, Stefano Cairo, Beate Häberle, Christian Vokuhl, Dietrich von Schweinitz, Roland Kappler
Hepatoblastoma (HB) is the most common liver tumor of childhood, usually occurring in children under the age of 3 y. The prognosis of patients presenting with distant metastasis, vascular invasion and advanced tumor stages remains poor and children that do survive often face severe late effects from the aggressive chemotherapy regimen. To identify potential new therapeutics for high risk HB we used a 1,000-gene expression signature as input for a Connectivity Map (CMap) analysis, which predicted histone deacetylase (HDAC) inhibitors as a promising therapy option...
September 16, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27635759/acetylation-dependent-control-of-global-poly-a-rna-degradation-by-cbp-p300-and-hdac1-2
#15
Sahil Sharma, Fabian Poetz, Marius Bruer, Thi Bach Nga Ly-Hartig, Johanna Schott, Bertrand Séraphin, Georg Stoecklin
Acetylation of histones and transcription-related factors is known to exert epigenetic and transcriptional control of gene expression. Here we report that histone acetyltransferases (HATs) and histone deacetylases (HDACs) also regulate gene expression at the posttranscriptional level by controlling poly(A) RNA stability. Inhibition of HDAC1 and HDAC2 induces massive and widespread degradation of normally stable poly(A) RNA in mammalian and Drosophila cells. Acetylation-induced RNA decay depends on the HATs p300 and CBP, which acetylate the exoribonuclease CAF1a, a catalytic subunit of the CCR4-CAF1-NOT deadenlyase complex and thereby contribute to accelerating poly(A) RNA degradation...
September 15, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27600599/histone-deacetylase-enzyme-silencing-using-shrnas-enhances-radiosensitivity-of-sw579-thyroid-cancer-cells
#16
Ye Wang, Tao Jin, Xueming Dai, Dongwang Yan, Zhihai Peng
The aim of the present study was to screen the enzymes that are associated with the radiosensitivity of SW579 thyroid cancer cells, and investigate whether radiation, combined with specific RNA interference on the screened enzymes, enhances radiosensitivity of SW579 thyroid cancer cells. Quantitative polymerase chain reaction (qPCR) was used to analyze epigenetic enzyme expression changes before and after radiotherapy, and four enzymes, histone deacetylase 1 (HDAC1), HDAC2, HDAC4 and HDAC6 were screened. Western blot analysis was performed to analyze the change in HDAC1, HDAC2, HDAC4 and HDAC6 protein expression following radiotherapy...
October 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27432453/hdac2-overexpression-is-a-poor-prognostic-factor-of-breast-cancer-patients-with-increased-multidrug-resistance-associated-protein-expression-who-received-anthracyclines-therapy
#17
Haishan Zhao, Zhaojin Yu, Lin Zhao, Miao He, Jie Ren, Huizhe Wu, Qiuchen Chen, Weifan Yao, Minjie Wei
OBJECTIVE: Previous studies have revealed the association of multidrug resistance with histone deacetylases inhibitors treatment in cancer cells. But little data were available for the correlation of histone deacetylases and drug-resistant-related proteins in breast cancer tissue. This study aimed to exploring the association of histone deacetylases expression with clinicopathological features, drug-resistant-related proteins, prognosis and therapeutic responses in breast cancer patients...
July 18, 2016: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27429844/therapeutic-intervention-of-silymarin-on-the-migration-of-non-small-cell-lung-cancer-cells-is-associated-with-the-axis-of-multiple-molecular-targets-including-class-1-hdacs-zeb1-expression-and-restoration-of-mir-203-and-e-cadherin-expression
#18
Tripti Singh, Ram Prasad, Santosh K Katiyar
Lung cancer and its metastasis is the leading cause of cancer-related mortality world-wide. Non-small cell lung cancer (NSCLC) accounts for about 90% of total lung cancer cases. Despite advancements in therapeutic approaches, only limited improvement has been achieved. Therefore, alternative strategies are required for the management of lung cancer. Here we report the chemotherapeutic effect of silymarin, a phytochemical from milk thistle plant (Silybum marianum L. Gaertn.), on NSCLC cell migration using metastatic human NSCLC cell lines (A549, H1299 and H460) together with the molecular targets underlying these effects...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27378074/loss-of-histone-deacetylase-hdac1-induces-cell-death-in-drosophila-epithelial-cells-through-jnk-and-hippo-signaling
#19
Tianyi Zhang, Zhentao Sheng, Wei Du
Inactivation of HDAC1 and its homolog HDAC2 or addition of HDAC inhibitors in mammalian systems induces apoptosis, cell cycle arrest, and developmental defects. Although these phenotypes have been extensively characterized, the precise underlying mechanisms remain unclear, particularly in in vivo settings. In this study, we show that inactivation of Rpd3, the only HDAC1 and HDAC2 ortholog in Drosophila, induced apoptosis and clone elimination in the developing eye and wing imaginal discs. Depletion of Rpd3 by RNAi cell-autonomously increased JNK activities and decreased activities of Yki, the nuclear effecter of Hippo signaling pathway...
August 2016: Mechanisms of Development
https://www.readbyqxmd.com/read/27377864/kinetic-and-structural-insights-into-the-binding-of-histone-deacetylase-1-and-2-hdac1-2-inhibitors
#20
Florence F Wagner, Michel Weïwer, Stefan Steinbacher, Adrian Schomburg, Peter Reinemer, Jennifer P Gale, Arthur J Campbell, Stewart L Fisher, Wen-Ning Zhao, Surya A Reis, Krista M Hennig, Méryl Thomas, Peter Müller, Martin R Jefson, Daniel M Fass, Stephen J Haggarty, Yan-Ling Zhang, Edward B Holson
The structure-activity and structure-kinetic relationships of a series of novel and selective ortho-aminoanilide inhibitors of histone deacetylases (HDACs) 1 and 2 are described. Different kinetic and thermodynamic selectivity profiles were obtained by varying the moiety occupying an 11Å channel leading to the Zn(2+) catalytic pocket of HDACs 1 and 2, two paralogs with a high degree of structural similarity. The design of these novel inhibitors was informed by two ligand-bound crystal structures of truncated hHDAC2...
September 15, 2016: Bioorganic & Medicinal Chemistry
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