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https://www.readbyqxmd.com/read/29163810/myeloid-ecotropic-viral-integration-site-1-inhibits-cell-proliferation-invasion-or-migration-in-human-gastric-cancer
#1
Fei Song, Hong Wang, Yingying Wang
Myeloid ecotropic viral integration site 1 (MEIS1) has been identified to be a potential tumor suppressor in some cancers. However, the mechanisms underlying MEIS1-induced cancer development and progression were not clear. Here, we investigated the expression and role of MEIS1 in gastric cancer. In vivo, we analyzed tumor growth using nude mice model. In the present study, MEIS1 expression was obviously decreased in GC cell lines compared with that in normal gastric cell lines (all p<0.001). MEIS1 overexpression inhibited cell proliferation and G1/S transition accompanied by decreased Cyclin D1 and Cyclin A expression...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29033051/genetics-of-restless-legs-syndrome-an-update
#2
REVIEW
Félix J Jiménez-Jiménez, Hortensia Alonso-Navarro, Elena García-Martín, José A G Agúndez
A major role of genetic factors in the risk of developing restless legs syndrome (RLS) is supported by the high frequency of positive family history of RLS in patients affected with this disease, and the higher concordance rates in monozygotic twins compared with dizygotic ones in twin studies. In this review we have focused on those reports describing inheritance patterns of RLS, genetic anticipation, the results of studies performed on positivity of family history of RLS, twin studies, linkage studies in familial RLS, genome-wide association studies (GWAS), exome sequencing studies, and case-control association studies on candidate genes in RLS...
August 31, 2017: Sleep Medicine Reviews
https://www.readbyqxmd.com/read/29029846/identification-of-novel-risk-loci-for-restless-legs-syndrome-in-genome-wide-association-studies-in-individuals-of-european-ancestry-a-meta-analysis
#3
REVIEW
Barbara Schormair, Chen Zhao, Steven Bell, Erik Tilch, Aaro V Salminen, Benno Pütz, Yves Dauvilliers, Ambra Stefani, Birgit Högl, Werner Poewe, David Kemlink, Karel Sonka, Cornelius G Bachmann, Walter Paulus, Claudia Trenkwalder, Wolfgang H Oertel, Magdolna Hornyak, Maris Teder-Laving, Andres Metspalu, Georgios M Hadjigeorgiou, Olli Polo, Ingo Fietze, Owen A Ross, Zbigniew Wszolek, Adam S Butterworth, Nicole Soranzo, Willem H Ouwehand, David J Roberts, John Danesh, Richard P Allen, Christopher J Earley, William G Ondo, Lan Xiong, Jacques Montplaisir, Ziv Gan-Or, Markus Perola, Pavel Vodicka, Christian Dina, Andre Franke, Lukas Tittmann, Alexandre F R Stewart, Svati H Shah, Christian Gieger, Annette Peters, Guy A Rouleau, Klaus Berger, Konrad Oexle, Emanuele Di Angelantonio, David A Hinds, Bertram Müller-Myhsok, Juliane Winkelmann
BACKGROUND: Restless legs syndrome is a prevalent chronic neurological disorder with potentially severe mental and physical health consequences. Clearer understanding of the underlying pathophysiology is needed to improve treatment options. We did a meta-analysis of genome-wide association studies (GWASs) to identify potential molecular targets. METHODS: In the discovery stage, we combined three GWAS datasets (EU-RLS GENE, INTERVAL, and 23andMe) with diagnosis data collected from 2003 to 2017, in face-to-face interviews or via questionnaires, and involving 15 126 cases and 95 725 controls of European ancestry...
November 2017: Lancet Neurology
https://www.readbyqxmd.com/read/29019697/development-of-potent-type-i-protein-arginine-methyltransferase-prmt-inhibitors-of-leukemia-cell-proliferation
#4
Chen Wang, Hao Jiang, Jia Jin, Yiqian Xie, Zhifeng Chen, Hao Zhang, Fulin Lian, Yu-Chih Liu, Chenhua Zhang, Hong Ding, Shijie Chen, Naixia Zhang, Yuanyuan Zhang, Hualiang Jiang, Kaixian Chen, Fei Ye, Zhiyi Yao, Cheng Luo
Protein Arginine Methyltransferases (PRMTs) are crucial players in diverse biological processes, and dysregulation of PRMTs has been linked to various human diseases, especially cancer. Therefore, small molecules targeting PRMTs have profound impact for both academic functional studies and clinical disease treatment. Here, we report the discovery of N(1)-(2-((2-chlorophenyl)thio)benzyl)-N(1)-methylethane-1,2-diamine (28d, DCPR049_12), a highly potent inhibitor of type I PRMTs that has good selectivity against a panel of other methyltransferases...
October 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28960191/meis2-as-a-critical-player-in-mn1-induced-leukemia
#5
C K Lai, G L Norddahl, T Maetzig, P Rosten, T Lohr, L Sanchez Milde, N von Krosigk, T R Docking, M Heuser, A Karsan, R K Humphries
Meningioma 1 (MN1) is an independent prognostic marker for normal karyotype acute myeloid leukemia (AML), with high expression linked to all-trans retinoic acid resistance and poor survival. MN1 is also a potent and sufficient oncogene in murine leukemia models, strongly dependent on the MEIS1/AbdB-like HOX protein complex to transform common myeloid progenitors, block myeloid differentiation, and promote leukemic stem cell self-renewal. To identify key genes and pathways underlying leukemic activity, we functionally assessed MN1 cell phenotypic heterogeneity, revealing leukemic and non-leukemic subsets...
September 29, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28956216/creb-nf-y-and-meis1-conserved-binding-sites-are-essential-to-balance-myostatin-promoter-enhancer-activity-during-early-myogenesis
#6
Carla Vermeulen Carvalho Grade, Carolina Stefano Mantovani, Marina Alves Fontoura, Faisal Yusuf, Beate Brand-Saberi, Lúcia Elvira Alvares
Myostatin (MSTN) is a strong inhibitor of skeletal muscle growth in human and other vertebrates. Its transcription is controlled by a proximal promoter/enhancer (Mstn P/E) containing a TATA box besides CREB, NF-Y, MEIS1 and FXR transcription factor binding sites (TFBSs), which are conserved throughout evolution. The aim of this work was to investigate the role of these TFBSs on Mstn P/E activity and evaluate the potential of their putative ligands as Mstn trans regulators. Mstn P/E mutant constructs were used to establish the role of conserved TFBSs using dual-luciferase assays...
October 2017: Molecular Biology Reports
https://www.readbyqxmd.com/read/28841467/chronological-age-prediction-based-on-dna-methylation-massive-parallel-sequencing-and-random-forest-regression
#7
Jana Naue, Huub C J Hoefsloot, Olaf R F Mook, Laura Rijlaarsdam-Hoekstra, Marloes C H van der Zwalm, Peter Henneman, Ate D Kloosterman, Pernette J Verschure
The use of DNA methylation (DNAm) to obtain additional information in forensic investigations showed to be a promising and increasing field of interest. Prediction of the chronological age based on age-dependent changes in the DNAm of specific CpG sites within the genome is one such potential application. Here we present an age-prediction tool for whole blood based on massive parallel sequencing (MPS) and a random forest machine learning algorithm. MPS allows accurate DNAm determination of pre-selected markers and neighboring CpG-sites to identify the best age-predictive markers for the age-prediction tool...
August 1, 2017: Forensic Science International. Genetics
https://www.readbyqxmd.com/read/28830460/gene-mutational-pattern-and-expression-level-in-560-acute-myeloid-leukemia-patients-and-their-clinical-relevance
#8
Yong-Mei Zhu, Pan-Pan Wang, Jin-Yan Huang, Yun-Shuo Chen, Bing Chen, Yu-Jun Dai, Han Yan, Yi Hu, Wen-Yan Cheng, Ting-Ting Ma, Sai-Juan Chen, Yang Shen
BACKGROUND: Cytogenetic aberrations and gene mutations have long been regarded as independent prognostic markers in AML, both of which can lead to misexpression of some key genes related to hematopoiesis. It is believed that the expression level of the key genes is associated with the treatment outcome of AML. METHODS: In this study, we analyzed the clinical features and molecular aberrations of 560 newly diagnosed non-M3 AML patients, including mutational status of CEBPA, NPM1, FLT3, C-KIT, NRAS, WT1, DNMT3A, MLL-PTD and IDH1/2, as well as expression levels of MECOM, ERG, GATA2, WT1, BAALC, MEIS1 and SPI1...
August 22, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28782694/co-regulation-of-micrornas-and-transcription-factors-in-cardiomyocyte-specific-differentiation-of-murine-embryonic-stem-cells-an-aspect-from-transcriptome-analysis
#9
Lin Gan, Bernd Denecke
The differentiation process of embryonic stem cells is a comprehensive process regulated by a variety of factors in response to stimulus. Studies of this process can be focused on cell biology as well as on molecular biology level. In this paper we identified the co-regulation of molecular regulators and their interactions during cardiomyocyte specific differentiation of mouse embryonic stem cells based on parallel genome wide transcriptome analyses of mRNA and microRNA. Differentially expressed mRNAs and microRNAs were identified according to their expression profiles...
September 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28751478/novel-gene-and-network-associations-found-for-acute-lymphoblastic-leukemia-using-case-control-and-family-based-studies-in-multiethnic-populations
#10
Priyanka Nakka, Natalie P Archer, Heng Xu, Philip J Lupo, Benjamin J Raphael, Jun J Yang, Sohini Ramachandran
Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, suggesting that germline variants influence ALL risk. Although multiple genome-wide association (GWA) studies have identified variants predisposing children to ALL, it remains unclear whether genetic heterogeneity affects ALL susceptibility and how interactions within and among genes containing ALL-associated variants influence ALL risk.Methods: Here, we jointly analyzed two published datasets of case-control GWA summary statistics along with germline data from ALL case-parent trios...
October 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28745213/emerging-roles-of-meis1-in-cardiac-regeneration-stem-cells-and-cancer
#11
Merve Aksoz, Raife Dilek Turan, Esra Albayrak, Fatih Kocabas
Meis1 is a member of three-amino-acid loop extension (TALE) homeodomain transcription factors. Studies in the last decade have shown that Meis1 has crucial roles in cardiac regeneration, stem cell function, and tumorigenesis. We have recently demonstrated that knocking out of Meis1 in adult cardiomyocytes resulted in the induction of cardiomyocyte proliferation. This suggests that targeting of Meis1 might be utilized in the manipulation of cardiomyocyte cell cycle post cardiac injuries. In addition, hematopoietic stem cell (HSC) specific deletion of Meis1 leads to in vivo expansion of HSCs pool...
July 24, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28735443/retinoic-acid-regulates-avian-lung-branching-through-a-molecular-network
#12
Hugo Fernandes-Silva, Patrícia Vaz-Cunha, Violina Baranauskaite Barbosa, Carla Silva-Gonçalves, Jorge Correia-Pinto, Rute Silva Moura
Retinoic acid (RA) is of major importance during vertebrate embryonic development and its levels need to be strictly regulated otherwise congenital malformations will develop. Through the action of specific nuclear receptors, named RAR/RXR, RA regulates the expression of genes that eventually influence proliferation and tissue patterning. RA has been described as crucial for different stages of mammalian lung morphogenesis, and as part of a complex molecular network that contributes to precise organogenesis; nonetheless, nothing is known about its role in avian lung development...
December 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28707666/-identification-of-proteins-associated-with-transcription-factors-hoxa9-and-e2a-pbx1-by-tandem-affinity-purification
#13
E A Shestakova, M Boutin, S Bourassa, E Bonneil, J J Bijl
Chimeric transcription factor E2A-PBX1 induces the development of acute lymphoblastic B-cell leukemia in children. Using a transgenic mouse model, we previously demonstrated that homeobox (HOX) gene HOXA9 genetically interact with E2A-PBX1 gene in the development of B-cell leukemia in mice. HOXA9 itself is a potent oncogene resulting in myeloid leukemia when overexpressed, which is strongly accelerated by its collaborator Meis1. HOX, PBX1 and MEIS1 proteins have been shown to form hetero dimeric or trimeric complexes in different combinations...
May 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28695622/sleep-disturbance-by-pramipexole-is-modified-by-meis1-in-mice
#14
Aaro V Salminen, Barbara Schormair, Cornelia Flachskamm, Miguel Torres, Bertram Müller-Myhsok, Mayumi Kimura, Juliane Winkelmann
Meis homeobox 1 (Meis1) is a transcription factor functioning in the development of the nervous system and the cardiovascular system. Both common and rare variants within the gene have been associated with restless legs syndrome (RLS), while its association with symptoms of insomnia has also been discovered recently. RLS is associated with sleep disturbances, and while Meis1 haploinsufficiency is one of the most promising strategies for an RLS animal model, sleep phenotyping of Meis1 knockout mice has never been conducted...
July 11, 2017: Journal of Sleep Research
https://www.readbyqxmd.com/read/28687780/nuclear-receptors-connect-progenitor-transcription-factors-to-cell-cycle-control
#15
Marta Neto, Marina Naval-Sánchez, Delphine Potier, Paulo S Pereira, Dirk Geerts, Stein Aerts, Fernando Casares
The specification and growth of organs is controlled simultaneously by networks of transcription factors. While the connection between these transcription factors with fate determinants is increasingly clear, how they establish the link with the cell cycle is far less understood. Here we investigate this link in the developing Drosophila eye, where two transcription factors, the MEIS1 homologue hth and the Zn-finger tsh, synergize to stimulate the proliferation of naïve eye progenitors. Experiments combining transcriptomics, open-chromatin profiling, motif analysis and functional assays indicate that these progenitor transcription factors exert a global regulation of the proliferation program...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28664166/lentiviral-fluorescent-genetic-barcoding-for-multiplex-fate-tracking-of-leukemic-cells
#16
Tobias Maetzig, Jens Ruschmann, Lea Sanchez Milde, Courteney K Lai, Niklas von Krosigk, R Keith Humphries
Tracking the behavior of leukemic samples both in vitro and in vivo plays an increasingly large role in efforts to better understand the leukemogenic processes and the effects of potential new therapies. Such work can be accelerated and made more efficient by methodologies enabling the characterization of leukemia samples in multiplex assays. We recently developed three sets of lentiviral fluorescent genetic barcoding (FGB) vectors that create 26, 14, and 6 unique immunophenotyping-compatible color codes from GFP-, yellow fluorescent protein (YFP)-, and monomeric kusabira orange 2 (mKO2)-derived fluorescent proteins...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28663367/genome-wide-temporal-profiling-of-transcriptome-and-open-chromatin-of-early-cardiomyocyte-differentiation-derived-from-hipscs-and-hescs
#17
Qing Liu, Chao Jiang, Jin Xu, Ming-Tao Zhao, Kevin Van Bortle, Xun Cheng, Guangwen Wang, Howard Y Chang, Joseph C Wu, Michael P Snyder
RATIONALE: Recent advances have improved our ability to generate cardiomyocytes from human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs). However, our understanding of the transcriptional regulatory networks underlying early stages (ie, from mesoderm to cardiac mesoderm) of cardiomyocyte differentiation remains limited. OBJECTIVE: To characterize transcriptome and chromatin accessibility during early cardiomyocyte differentiation from hiPSCs and hESCs...
August 4, 2017: Circulation Research
https://www.readbyqxmd.com/read/28645892/meis1-effects-on-motor-phenotypes-and-the-sensorimotor-system-in-mice
#18
Aaro V Salminen, Lillian Garrett, Barbara Schormair, Jan Rozman, Florian Giesert, Kristina M Niedermeier, Lore Becker, Birgit Rathkolb, Ildikó Rácz, Martin Klingenspor, Thomas Klopstock, Eckhard Wolf, Andreas Zimmer, Valérie Gailus-Durner, Miguel Torres, Helmut Fuchs, Martin Hrabě de Angelis, Wolfgang Wurst, Sabine M Hölter, Juliane Winkelmann
MEIS1 encodes a developmental transcription factor and has been linked to restless legs syndrome (RLS) in genome-wide association studies. RLS is a movement disorder leading to severe sleep reduction and has a substantial impact on the quality of life of patients. In genome-wide association studies, MEIS1 has consistently been the gene with the highest effect size and functional studies suggest a disease-relevant downregulation. Therefore, haploinsufficiency of Meis1 could be the system with the most potential for modeling RLS in animals...
August 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28626420/restless-legs-syndrome-from-pathophysiology-to-clinical-diagnosis-and-management
#19
REVIEW
Shiyi Guo, Jinsha Huang, Haiyang Jiang, Chao Han, Jie Li, Xiaoyun Xu, Guoxin Zhang, Zhicheng Lin, Nian Xiong, Tao Wang
Restless legs syndrome (RLS), a common neurological sensorimotor disorder in western countries, has gained more and more attention in Asian countries. The prevalence of RLS is higher in older people and females. RLS is most commonly related to iron deficiency, pregnancy and uremia. The RLS symptoms show a significant circadian rhythm and a close relationship to periodic limb movements (PLMs) in clinical observations, while the pathophysiological pathways are still unknown. The diagnostic criteria have been revised in 2012 to improve the validity of RLS diagnosis...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28604731/genome-wide-association-analysis-of-insomnia-complaints-identifies-risk-genes-and-genetic-overlap-with-psychiatric-and-metabolic-traits
#20
Anke R Hammerschlag, Sven Stringer, Christiaan A de Leeuw, Suzanne Sniekers, Erdogan Taskesen, Kyoko Watanabe, Tessa F Blanken, Kim Dekker, Bart H W Te Lindert, Rick Wassing, Ingileif Jonsdottir, Gudmar Thorleifsson, Hreinn Stefansson, Thorarinn Gislason, Klaus Berger, Barbara Schormair, Juergen Wellmann, Juliane Winkelmann, Kari Stefansson, Konrad Oexle, Eus J W Van Someren, Danielle Posthuma
Persistent insomnia is among the most frequent complaints in general practice. To identify genetic factors for insomnia complaints, we performed a genome-wide association study (GWAS) and a genome-wide gene-based association study (GWGAS) in 113,006 individuals. We identify three loci and seven genes associated with insomnia complaints, with the associations for one locus and five genes supported by joint analysis with an independent sample (n = 7,565). Our top association (MEIS1, P < 5 × 10(-8)) has previously been implicated in restless legs syndrome (RLS)...
November 2017: Nature Genetics
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