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https://www.readbyqxmd.com/read/28723562/integrative-genomics-identifies-the-molecular-basis-of-resistance-to-azacitidine-therapy-in-myelodysplastic-syndromes
#1
Ashwin Unnikrishnan, Elli Papaemmanuil, Dominik Beck, Nandan P Deshpande, Arjun Verma, Ashu Kumari, Petter S Woll, Laura A Richards, Kathy Knezevic, Vashe Chandrakanthan, Julie A I Thoms, Melinda L Tursky, Yizhou Huang, Zara Ali, Jake Olivier, Sally Galbraith, Austin G Kulasekararaj, Magnus Tobiasson, Mohsen Karimi, Andrea Pellagatti, Susan R Wilson, Robert Lindeman, Boris Young, Raj Ramakrishna, Christopher Arthur, Richard Stark, Philip Crispin, Jennifer Curnow, Pauline Warburton, Fernando Roncolato, Jacqueline Boultwood, Kevin Lynch, Sten Eirik W Jacobsen, Ghulam J Mufti, Eva Hellstrom-Lindberg, Marc R Wilkins, Karen L MacKenzie, Jason W H Wong, Peter J Campbell, John E Pimanda
Myelodysplastic syndromes and chronic myelomonocytic leukemia are blood disorders characterized by ineffective hematopoiesis and progressive marrow failure that can transform into acute leukemia. The DNA methyltransferase inhibitor 5-azacytidine (AZA) is the most effective pharmacological option, but only ∼50% of patients respond. A response only manifests after many months of treatment and is transient. The reasons underlying AZA resistance are unknown, and few alternatives exist for non-responders. Here, we show that AZA responders have more hematopoietic progenitor cells (HPCs) in the cell cycle...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28706212/epigenetics-of-the-preferential-silencing-of-brachypodium-stacei-originated-35s-rdna-loci-in-the-allotetraploid-grass-brachypodium-hybridum
#2
Natalia Borowska-Zuchowska, Robert Hasterok
Nucleolar dominance (ND), initially described as 'differential amphiplasty', is a phenomenon observed in some plant and animal allopolyploids and hybrids in which the selective suppression of the activity of 35S rRNA gene loci that have been inherited from one of the two or more ancestral genomes occurs. Although more than 80 years have passed since the discovery of ND, there is still a significant lack in our understanding of the mechanisms that determine this phenomenon. Here, we aimed to investigate the epigenetic status of 35S rRNA gene loci in the monocotyledonous Brachypodium hybridum, which is an allotetraploid that has resulted from a cross between B...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28694421/kr%C3%A3-ppel-like-factor-4-enhances-sensitivity-of-cisplatin-to-esophageal-squamous-cell-carcinoma-escc-cells
#3
Chuangui Chen, Zhao Ma, Hongdian Zhang, Xiaoqiong Liu, Zhentao Yu
BACKGROUND The aim of this study was to elucidate the role of Krüppel-Like factor 4 (KLF4) in cisplatin resistance in esophageal squamous cell carcinoma (ESCC) cells, which may eventually help to improve the treatment efficacy. MATERIAL AND METHODS Human esophageal squamous cell carcinoma (ESCC) cell line CaEs-17, TE-1, EC109, KYSE510, KYSE140, KYSE70, and KYSE30 were selected to detect their sensitivity to cisplatin. 5-Azacytidine-2'-deoxycytidine (5'-Aza-CdR) treatment and methylation-specific PCR (MS-PCR) were used to detect the methylation status for KLF4...
July 11, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28684528/wnt-%C3%A3-catenin-activation-by-epigenetically-aberrant-stroma-drives-myelodysplastic-syndrome
#4
Tushar Bhagat, Si Chen, Matthias Bartenstein, Trevor S Barlowe, Dagny von Ahrens, Gaurav S Choudhary, Patrick Tivnan, Elianna Amin, A Mario Marcondes, Mathijs A Sanders, Remco M Hoogenboezem, Suman Kambhampati, Nandini Ramachandra, Ioannis Mantzaris, Vineeth Sukrithan, Remi Laurence, Robert Lopez, Prafulla Bhagat, Orsi Giricz, Davendra Sohal, Amittha Wickrema, Cecilia Cs Yeung, Kira Gritsman, Peter D Aplan, Konrad Hochedlinger, Yiting Yu, Kith Pradhan, Jinghang Zhang, John Greally, Siddhartha Mukherjee, Andrea Pellagatti, Jacqueline Boultwood, Britta Will, Ulrich Steidl, Marc Hgp Raaijmakers, H J Deeg, Michael G Kharas, Amit Verma
The bone marrow microenvironment influences malignant hematopoiesis but how it promotes leukemogenesis has not been elucidated. Additionally, the role of the bone marrow stroma in regulating clinical responses to DNA methyltransferase inhibitors (DNMTi) is also poorly understood. In this study, we conducted a DNA methylome analysis of bone marrow-derived stromal cells from myelodysplastic syndrome (MDS) patients and observed widespread aberrant cytosine hypermethylation occurring preferentially outside CpG islands...
July 6, 2017: Cancer Research
https://www.readbyqxmd.com/read/28677769/valproic-acid-enforces-the-priming-effect-of-sphingosine-1-phosphate-on-human-mesenchymal-stem-cells
#5
Jisun Lim, Seungun Lee, Hyein Ju, Yonghwan Kim, Jinbeom Heo, Hye-Yeon Lee, Kyung-Chul Choi, Jaekyoung Son, Yeon-Mok Oh, In-Gyu Kim, Dong-Myung Shin
Engraftment and homing of mesenchymal stem cells (MSCs) are modulated by priming factors including the bioactive lipid sphingosine-1-phosphate (S1P), by stimulating CXCR4 receptor signaling cascades. However, limited in vivo efficacy and the remaining priming molecules prior to administration of MSCs can provoke concerns regarding the efficiency and safety of MSC priming. Here, we showed that valproic acid (VPA), a histone deacetylase inhibitor, enforced the priming effect of S1P at a low dosage for human umbilical cord-derived MSCs (UC-MSCs)...
July 3, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28669364/expression-of-markers-for-germ-cells-and-oocytes-in-cow-dermal-fibroblast-treated-with-5-azacytidine-and-cultured-in-differentiation-medium-containing-bmp2-bmp4-or-follicular-fluid
#6
José Jackson do Nascimento Costa, Glaucinete Borges de Souza, Joyla Maria Pires Bernardo, Regislane Pinto Ribeiro, José Renato de Souza Passos, Francisco Taiã Gomes Bezerra, Márcia Viviane Alves Saraiva, José Roberto Viana Silva
This study aims to investigate the effect 5-azacytidine (5-Aza) during induction of pluripotency in bovine fibroblasts and to evaluate the effects of BMP2, BMP4 or follicular fluid in the differentiation of reprogrammed fibroblasts in primordial germ cells and oocytes. It also analysis the mRNA levels for OCT4, NANOG, REX, SOX2, VASA, DAZL, cKIT, SCP3, ZPA and GDF9 after culturing 5-Aza treated fibroblasts in the different tested medium. Dermal fibroblasts were cultured and exposed to 0.5, 1.0 or 2.0 μM of 5-Aza for 18 h, 36 h or 72 h...
July 3, 2017: Zygote: the Biology of Gametes and Early Embryos
https://www.readbyqxmd.com/read/28663119/minimal-traumatic-brain-injury-causes-persistent-changes-in-dna-methylation-at-bdnf-gene-promoters-in-rat-amygdala-a-possible-role-in-anxiety-like-behaviors
#7
Sneha Sagarkar, Tanmayi Bhamburkar, Gajanan Shelkar, Amit Choudhary, Dadasaheb M Kokare, Amul J Sakharkar
Minimal traumatic brain injury (MTBI) often transforms into chronic neuropsychiatric conditions including anxiety, the underlying mechanisms of which are largely unknown. In the present study, we employed the closed-head injury paradigm to induce MTBI in rats and examined whether DNA methylation can explain long-term changes in the expression of the brain-derived neurotrophic factor (BDNF) in the amygdala as well as trauma-induced anxiety-like behaviors. The MTBI caused anxiety-like behaviors and altered the expression of DNA methyltransferase (DNMT) isoforms (DNMT1, DNMT3a, and DNMT3b) and factors involved in DNA demethylation such as the growth arrest and DNA damage 45 (GADD45a and GADD45b)...
June 27, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28644148/5-azacytidine-promotes-invadopodia-formation-and-tumor-metastasis-through-the-upregulation-of-pi3k-in-ovarian-cancer-cells
#8
Dan Cao, Dan Li, Yong Huang, Yu Ma, Binglan Zhang, Chengjian Zhao, Senyi Deng, Min Luo, Tao Yin, Yu-Quan Wei, Wei Wang
The high incidence of metastasis accounts for most of the lethality of ovarian cancer. Invadopodia are small, specialized types of machinery that degrade the extracellular matrix and are thus involved in the invasion and metastasis of cancer cells. The formation of invadopodia is regulated by both genetic and epigenetic factors. However, the ways by which methylation/demethylation regulates the dynamics of invadopodia in ovarian cancer are largely unknown. In this study, we found that the inhibition of methylation by 5-AZ (5-Azacytidine) increased the formation of invadopodia and enhanced degradation of the extracellular matrix in ovarian cancer cells...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28638744/azacytidine-prevents-experimental-xenogeneic-graft-versus-host-disease-without-abrogating-graft-versus-leukemia-effects
#9
Grégory Ehx, Gilles Fransolet, Laurence de Leval, Stéphanie D'Hondt, Sophie Lucas, Muriel Hannon, Loïc Delens, Sophie Dubois, Pierre Drion, Yves Beguin, Stéphanie Humblet-Baron, Frédéric Baron
The demethylating agent 5-azacytidine (AZA) has proven its efficacy in the treatment of myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading to the generation of regulatory T cells (Treg). Here, we investigated the impact of AZA on xenogeneic graft-vs.-host disease (xGVHD) and graft-vs.-leukemia effects in a humanized murine model of transplantation (human PBMCs-infused NSG mice), and described the impact of the drug on human T cells in vivo...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28607150/wnt3a-induces-the-expression-of-acetylcholinesterase-during-osteoblast-differentiation-via-the-runx2-transcription-factor
#10
Miranda L Xu, Cathy W C Bi, Etta Y L Liu, Tina T X Dong, Karl W K Tsim
Acetylcholinesterase (AChE) hydrolyzes acetylcholine to terminate cholinergic transmission in neurons. Apart from this AChE activity, emerging evidence suggests that AChE could also function in other, nonneuronal cells. For instance, in bone, AChE exists as a proline-rich membrane anchor (PRiMA)-linked globular form in osteoblasts, in which it is proposed to play a noncholinergic role in differentiation. However, this hypothesis is untested. Here, we found that in cultured rat osteoblasts, AChE expression was increased in parallel with osteoblastic differentiation...
June 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28601197/a-comparative-study-to-evaluate-myogenic-differentiation-potential-of-human-chorion-versus-umbilical-cord-blood-derived-mesenchymal-stem-cells
#11
Nikoo Bana, Davood Sanooghi, Mansoureh Soleimani, Nasim Hayati Roodbari, Sepideh Alavi Moghaddam, Mohammad Taghi Joghataei, Forough Azam Sayahpour, Faezeh Faghihi
OBJECTIVE: Musculodegenerative diseases threaten the life of many patients in the world. Since drug administration is not efficient in regeneration of damaged tissues, stem cell therapy is considered as a good strategy to restore the lost cells. Since the efficiency of myogenic differentiation potential of human Chorion- derived Mesenchymal Stem Cells (C-MSCs) has not been addressed so far; we set out to evaluate myogenic differentiation property of these cells in comparison with Umbilical Cord Blood- derived Mesenchymal Stem Cells (UCB-MSCs) in the presence of 5-azacytidine...
May 11, 2017: Tissue & Cell
https://www.readbyqxmd.com/read/28586038/mir-1247-5p-functions-as-a-tumor-suppressor-in-human-hepatocellular-carcinoma-by-targeting-wnt3
#12
Yuankui Chu, Weining Fan, Wenwei Guo, Yixin Zhang, Lixin Wang, Le Guo, Xiangguo Duan, Jun Wei, Guangxian Xu
Increasing evidence suggests that aberrant expression of certain microRNAs (miRNAs) may participate in the genesis and progression of tumors. Several studies have indicated that miR-1247-5p plays different roles in various types of cancer cells. The effects of miR-1247-5p on human hepatocellular carcinoma (HCC) cells are elusive. In the present study, we investigated the effects of miR-1247-5p on the progression of HCC. The transcript of miR-1247-5p was markedly downregulated in clinical samples of patients with HCC and HCC cell lines, and ectopic overexpression of miR‑1247-5p markedly inhibited the proliferation and invasion of HepG2 cells, induced cell apoptosis in vitro, and suppressed the growth of transplanted tumors in vivo...
June 6, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28575160/dynamic-changes-in-methylome-and-transcriptome-patterns-in-response-to-methyltransferase-inhibitor-5-azacytidine-treatment-in-citrus
#13
Jidi Xu, Xia Wang, Hongbo Cao, Haidan Xu, Qiang Xu, Xiuxin Deng
DNA methylation is known to play an important role in various developmental processes in plants. However, there is a general lack of understanding about the possible functions of DNA methylation in fruit trees. Using callus as a model, methylome, transcriptome and metabolite changes were assessed after treatment with the DNA methyltransferase inhibitor 5-azacytidine (5azaC). Genome-wide methylome analysis revealed the demethylation of a diverse of genes, including many genes encoding transcription factors (TFs), genes involved in biological processes, and the up-regulation of a wide range of transposable elements (TEs)...
June 1, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/28543390/the-effect-of-ebv-on-wif1-nlk-and-apc-gene-methylation-and-expression-in-gastric-carcinoma-and-nasopharyngeal-cancer
#14
Zhenzhen Zhao, Wen Liu, Jincheng Liu, Jiayi Wang, Bing Luo
Epstein-Barr virus (EBV) is an important DNA tumor virus that is associated with approximately 10% of gastric carcinomas and 99% of nasopharyngeal cancers. DNA methylation and microRNAs (miRNAs) are the most studied epigenetic mechanisms that can prompt disease susceptibility. This study aimed to detect the effect of EBV on Wnt inhibitory factor 1 (WIF1), Nemo-like kinase (NLK), and adenomatous polyposis coli (APC) gene methylation and expression in gastric carcinoma and nasopharyngeal cancer. METHODS: The WIF1, NLK, and APC gene mRNA expression levels were measured by real-time quantitative RT-PCR in four EBV-positive cell lines and four EBV-negative cell lines...
May 23, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28529454/characterization-of-cytosine-methylation-and-the-dna-methyltransferases-of-toxoplasma-gondii
#15
Haixia Wei, Shichen Jiang, Longfei Chen, Cheng He, Shuizhen Wu, Hongjuan Peng
DNA methylation is a key epigenetic modification which confers phenotypic plasticity and adaptation. Cyst-forming strains of Toxoplasma gondii undergo tachyzoite to bradyzoite conversion after initial acute infection of a host, and the reverse conversion may occur in immune-suppressed hosts. The formation of m(5)C is catalyzed by DNA methyltransferase (DNMT). We identified two functional DNA methyltransferases, TgDNMTa and TgDNMTb, in T. gondii that may mediate DNA methylation. The recombinant proteins showed intrinsic methyltransferase activity; both have higher transcription levels in bradyzoites than that in tachyzoites...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28527889/enhanced-cardiomyogenic-induction-of-mouse-pluripotent-cells-by-cyclic-mechanical-stretch
#16
Akankshya Shradhanjali, Brandon D Riehl, Jeong Soon Lee, Ligyeom Ha, Jung Yul Lim
The cardiac milieu is mechanically active with spontaneous contraction beginning from early development and persistent through maturation and homeostasis, suggesting that mechanical loading may provide a biomimetic myocardial developmental signal. In this study, we tested the role of cyclic mechanical stretch loading in the cardiomyogenesis of pluripotent murine embryonic (P19) stem cells. A Flexcell tension system was utilized to apply equiaxial stretch (12% strain, 1.25 Hz frequency) to P19 cell-derived embryoid bodies (EBs)...
May 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28512793/5-azacytidine-mediated-hmsc-behavior-on-electrospun-scaffolds-for-skeletal-muscle-regeneration
#17
Ines Fasolino, Vincenzo Guarino, Valentina Cirillo, Luigi Ambrosio
Incomplete regeneration after trauma or muscular dysfunction is a common problem in muscle replacement therapies. Recent approaches in tissue engineering allow for the replication of skeletal muscle structure and function in vitro and in vivo by molecular therapies and implantable scaffolds which properly address muscle cells toward myotube differentiation and maturation. Here, we investigate the in vitro response of human mesenchymal stem cells (hMSC) on electrospun fibers made of polycaprolactone (PCL) in the presence of 5-azacytidine (5-AZA) to evaluate how fibrous network may influence the therapeutic effect of drug during in vitro myogenesis...
May 16, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28510781/5-azacytidine-mediated-reactivation-of-silenced-transgenes-in-potato-solanum-tuberosum-at-the-whole-plant-level
#18
Dimitrij Tyč, Eva Nocarová, Lenka Sikorová, Lukáš Fischer
Transient 5-azacytidine treatment of leaf explants from potato plants with transcriptionally silenced transgenes allows de novo regeneration of plants with restored transgene expression at the whole plant level. Transgenes introduced into plant genomes frequently become silenced either at the transcriptional or the posttranscriptional level. Transcriptional silencing is usually associated with DNA methylation in the promoter region. Treatments with inhibitors of maintenance DNA methylation were previously shown to allow reactivation of transcriptionally silenced transgenes in single cells or tissues, but not at the whole plant level...
August 2017: Plant Cell Reports
https://www.readbyqxmd.com/read/28510608/the-biomphalaria-glabrata-dna-methylation-machinery-displays-spatial-tissue-expression-is-differentially-active-in-distinct-snail-populations-and-is-modulated-by-interactions-with-schistosoma-mansoni
#19
Kathrin K Geyer, Umar H Niazi, David Duval, Céline Cosseau, Chad Tomlinson, Iain W Chalmers, Martin T Swain, David J Cutress, Utibe Bickham-Wright, Sabrina E Munshi, Christoph Grunau, Timothy P Yoshino, Karl F Hoffmann
BACKGROUND: The debilitating human disease schistosomiasis is caused by infection with schistosome parasites that maintain a complex lifecycle alternating between definitive (human) and intermediate (snail) hosts. While much is known about how the definitive host responds to schistosome infection, there is comparably less information available describing the snail's response to infection. METHODOLOGY/PRINCIPLE FINDINGS: Here, using information recently revealed by sequencing of the Biomphalaria glabrata intermediate host genome, we provide evidence that the predicted core snail DNA methylation machinery components are associated with both intra-species reproduction processes and inter-species interactions...
May 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28490812/hdac3-regulates-dnmt1-expression-in-multiple-myeloma-therapeutic-implications
#20
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
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