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https://www.readbyqxmd.com/read/28334814/genome-wide-association-study-identifies-novel-susceptible-loci-and-highlights-wnt-beta-catenin-pathway-in-the-development-of-adolescent-idiopathic-scoliosis
#1
Zezhang Zhu, Leilei Xu, Nelson Leung-Sang Tang, Xiaodong Qin, Zhenhua Feng, Weixiang Sun, Weiguo Zhu, Benlong Shi, Peng Liu, Saihu Mao, Jun Qiao, Zhen Liu, Xu Sun, Fangcai Li, Jack Chun-Yiu Cheng, Yong Qiu
The genetic architecture of adolescent idiopathic scoliosis (AIS) remains poorly understood. Here we present the result of a 4-stage genome-wide association study composed of 5,953 AIS patients and 8,137 controls. Overall, we identified three novel susceptible loci including rs7593846 at 2p14 near MEIS1 (Pcombined = 1.19 × 10-13, OR = 1.21, 95% CI = 1.10-1.32), rs7633294 at 3p14.1 near MAGI1 (Pcombined = 1.85 × 10-12, OR = 1.20, 95% CI = 1.09-1.32), and rs9810566 at 3q26.2 near TNIK (Pcombined = 1...
February 28, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28329290/association-of-btbd9-and-map2k5-skor1-with-restless-legs-syndrome-in-chinese-population
#2
Gen Li, Huidong Tang, Cheng Wang, Xuemei Qi, Jie Chen, Shengdi Chen, Jianfang Ma
Objective: The aim of the study was to investigate the relationship between genetic factors and primary restless legs syndrome (RLS) in Chinese population. Methods: Totally, 116 RLS patients and 200 controls were recruited and the diagnosis of RLS was based on the criteria of International RLS Study Group. Polymer chain reaction (PCR) and sequencing were used to detect 19 single nucleotide polymorphisms (SNPs) in six genetic loci (MEIS1, BTBD9, PTPRD, MAP2K5/SKOR1, TOX3, and Intergenic region of 2p14)...
February 24, 2017: Sleep
https://www.readbyqxmd.com/read/28322463/a-tale-of-tale-prep1-pbx1-and-meis1-interconnections-and-competition-in-cancer
#3
REVIEW
Francesco Blasi, Chiara Bruckmann, Dmitry Penkov, Leila Dardaei
We report the latest structural information on PREP1 tumor suppressor, the specific "oncogene" and "tumor suppressive" signatures of MEIS1 and PREP1, the molecular rules regulating PREP1 and MEIS1 binding to DNA, and how these can change depending on the interaction with PBX1, cell-type, neoplastic transformation, and intracellular concentration. As both PREP1 and MEIS1 interact with PBX1 they functionally compete with each other. PREP1, PBX1, and MEIS1 TALE-class homeodomain transcription factors act in an interdependent and integrated way in experimental tumorigenesis...
March 21, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28288143/dnmt3a-mutations-mediate-the-epigenetic-reactivation-of-the-leukemogenic-factor-meis1-in-acute-myeloid-leukemia
#4
H J Ferreira, H Heyn, M Vizoso, C Moutinho, E Vidal, A Gomez, A Martínez-Cardús, L Simó-Riudalbas, S Moran, E Jost, M Esteller
No abstract text is available yet for this article.
March 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28270206/meis1-inhibits-clear-cell-renal-cell-carcinoma-cells-proliferation-and-in-vitro-invasion-or-migration
#5
Jie Zhu, Liang Cui, Axiang Xu, Xiaotao Yin, Fanglong Li, Jiangping Gao
BACKGROUND: Myeloid ecotropic viral integration site 1 (MEIS1) protein plays a synergistic causative role in acute myeloid leukemia (AML). However, MEIS1 has also shown to be a potential tumor suppressor in some other cancers, such as non-small-cell lung cancer (NSCLC) and prostate cancer. Although multiple roles of MEIS1 in cancer development and progression have been identified, there is an urgent demand to discover more functions of this molecule for further therapeutic design. METHODS: MEIS1 was overexpressed via adenovirus vector in clear cell renal cell carcinoma (ccRCC) cells...
March 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28236139/iron-dopamine-genetics-and-hormones-in-the-pathophysiology-of-restless-legs-syndrome
#6
REVIEW
Farhan H Khan, Caitlyn D Ahlberg, Christopher A Chow, Divya R Shah, Brian B Koo
Restless legs syndrome (RLS) is a common, chronic neurologic condition, which causes a persistent urge to move the legs in the evening that interferes with sleep. Human and animal studies have been used to study the pathophysiologic state of RLS and much has been learned about the iron and dopamine systems in relation to RLS. Human neuropathologic and imaging studies have consistently shown decreased iron in different brain regions including substantia nigra and thalamus. These same areas also demonstrate a state of relative dopamine excess...
February 24, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28229434/preclinical-pharmacokinetics-and-pharmacodynamics-of-pinometostat-epz-5676-a-first-in-class-small-molecule-s-adenosyl-methionine-competitive-inhibitor-of-dot1l
#7
Nigel J Waters
Acute leukemias bearing mixed lineage leukemia (MLL) rearrangements are aggressive diseases characterized by a poor overall prognosis despite multi-agent chemotherapy. Aberrant fusion proteins involving the MLL histone methyltransferase (HMT) lead to recruitment of DOT1L, to a multi-protein complex resulting in aberrant methylation of histone H3 lysine 79 at MLL target genes, and ultimately enhanced expression of critical genes for hematopoietic differentiation, including HOXA9 and MEIS1, and as such defines the established mechanism for leukemogenesis in MLL-rearrangement (MLL-r) leukemias...
February 22, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28202494/fumarate-hydratase-is-a-critical-metabolic-regulator-of-hematopoietic-stem-cell-functions
#8
Amelie V Guitart, Theano I Panagopoulou, Arnaud Villacreces, Milica Vukovic, Catarina Sepulveda, Lewis Allen, Roderick N Carter, Louie N van de Lagemaat, Marcos Morgan, Peter Giles, Zuzanna Sas, Marta Vila Gonzalez, Hannah Lawson, Jasmin Paris, Joy Edwards-Hicks, Katrin Schaak, Chithra Subramani, Deniz Gezer, Alejandro Armesilla-Diaz, Jimi Wills, Aaron Easterbrook, David Coman, Chi Wai Eric So, Donal O'Carroll, Douglas Vernimmen, Neil P Rodrigues, Patrick J Pollard, Nicholas M Morton, Andrew Finch, Kamil R Kranc
Strict regulation of stem cell metabolism is essential for tissue functions and tumor suppression. In this study, we investigated the role of fumarate hydratase (Fh1), a key component of the mitochondrial tricarboxylic acid (TCA) cycle and cytosolic fumarate metabolism, in normal and leukemic hematopoiesis. Hematopoiesis-specific Fh1 deletion (resulting in endogenous fumarate accumulation and a genetic TCA cycle block reflected by decreased maximal mitochondrial respiration) caused lethal fetal liver hematopoietic defects and hematopoietic stem cell (HSC) failure...
March 6, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28054140/meis1-is-critical-to-the-maintenance-of-human-acute-myeloid-leukemia-cells-independent-of-mll-rearrangements
#9
Jiangying Liu, Ya-Zhen Qin, Shenmiao Yang, Yazhe Wang, Ying-Jun Chang, Ting Zhao, Qian Jiang, Xiao-Jun Huang
Although the outcome of patients with acute myeloid leukemia (AML) has improved by optimized chemotherapy regimens and bone marrow transplantation, leukemia relapse remains one of the most challenging problems during therapy. Sustained existence of AML blasts is a fundamental determinant for the development of leukemia and resistance to therapy. Recent evidences suggest that Meis1 is tightly associated with the self-renewal capacity of normal hematopoietic stem cells. Meis1 was also found to be essential for the development of mixed lineage leukemia (MLL)-rearranged leukemia...
April 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28049638/leukemic-blasts-program-bone-marrow-adipocytes-to-generate-a-pro-tumoral-microenvironment
#10
Manar S Shafat, Thomas Oellerich, Sebastian Mohr, Stephen D Robinson, Dylan R Edwards, Christopher R Marlein, Rachel E Piddock, Matthew Fenech, Lyubov Zaitseva, Amina Abdul-Aziz, Jeremy Turner, Johnathan A Watkins, Matthew Lawes, Kristian M Bowles, Stuart A Rushworth
Despite currently available therapies most patients diagnosed with acute myeloid leukemia (AML) die of their disease. Tumor-host interactions are critical for the survival and proliferation of cancer cells; accordingly, we hypothesise that specific targeting of the tumor microenvironment may constitute an alternative or additional strategy to conventional tumor-directed chemotherapy. Since adipocytes have been shown to promote breast and prostate cancer proliferation, and because the bone marrow adipose tissue (MAT) accounts for up to 70% of bone marrow volume in adult humans, we examined the adipocyte-leukaemia cell interactions to determine if they are essential for the growth and survival of AML...
January 3, 2017: Blood
https://www.readbyqxmd.com/read/27992416/genome-wide-association-analyses-of-sleep-disturbance-traits-identify-new-loci-and-highlight-shared-genetics-with-neuropsychiatric-and-metabolic-traits
#11
Jacqueline M Lane, Jingjing Liang, Irma Vlasac, Simon G Anderson, David A Bechtold, Jack Bowden, Richard Emsley, Shubhroz Gill, Max A Little, Annemarie I Luik, Andrew Loudon, Frank A J L Scheer, Shaun M Purcell, Simon D Kyle, Deborah A Lawlor, Xiaofeng Zhu, Susan Redline, David W Ray, Martin K Rutter, Richa Saxena
Chronic sleep disturbances, associated with cardiometabolic diseases, psychiatric disorders and all-cause mortality, affect 25-30% of adults worldwide. Although environmental factors contribute substantially to self-reported habitual sleep duration and disruption, these traits are heritable and identification of the genes involved should improve understanding of sleep, mechanisms linking sleep to disease and development of new therapies. We report single- and multiple-trait genome-wide association analyses of self-reported sleep duration, insomnia symptoms and excessive daytime sleepiness in the UK Biobank (n = 112,586)...
December 19, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27918583/the-gene-regulatory-network-of-lens-induction-is-wired-through-meis-dependent-shadow-enhancers-of-pax6
#12
Barbora Antosova, Jana Smolikova, Lucie Klimova, Jitka Lachova, Michaela Bendova, Iryna Kozmikova, Ondrej Machon, Zbynek Kozmik
Lens induction is a classical developmental model allowing investigation of cell specification, spatiotemporal control of gene expression, as well as how transcription factors are integrated into highly complex gene regulatory networks (GRNs). Pax6 represents a key node in the gene regulatory network governing mammalian lens induction. Meis1 and Meis2 homeoproteins are considered as essential upstream regulators of Pax6 during lens morphogenesis based on their interaction with the ectoderm enhancer (EE) located upstream of Pax6 transcription start site...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27795845/epigenetics-of-ancient-dna
#13
S V Zhenilo, A S Sokolov, E B Prokhortchouk
Initially, the study of DNA isolated from ancient specimens had been based on the analysis of the primary nucleotide sequence. This approach has allowed researchers to study the evolutionary changes that occur in different populations and determine the influence of the environment on genetic selection. However, the improvement of methodological approaches to genome-wide analysis has opened up new possibilities in the search for the epigenetic mechanisms involved in the regulation of gene expression. It was discovered recently that the methylation status of the regulatory elements of the HOXD cluster and MEIS1 gene changed during human evolution...
July 2016: Acta Naturae
https://www.readbyqxmd.com/read/27748908/cardioprotective-potential-of-dendrobium%C3%A2-officinale-kimura-et-migo-against-myocardial-ischemia-in-mice
#14
Meng-Meng Dou, Zhi-Hao Zhang, Zhu-Bo Li, Jie Zhang, Xiao-Yan Zhao
Dendrobium officinale Kimura et Migo has been used for thousands of years to promote body fluid production; however, little is currently known regarding its effects on the heart. The present study aimed to explore the cardioprotective potential of the water extract of Dendrobium officinale Kimura et Migo (DOE) on myocardial ischemia in mice. A mouse model of myocardial ischemia was induced following ligation of the left anterior descending coronary artery. Prior to the operation, mice were administered a vehicle or DOE for 2 weeks...
November 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27619068/microrna-155-is-upregulated-in-mll-rearranged-aml-but-its-absence-does-not-affect-leukemia-development
#15
Edith Schneider, Anna Staffas, Linda Röhner, Kathrin Krowiorz, Michael Heuser, Konstanze Döhner, Lars Bullinger, Hartmut Döhner, Linda Fogelstrand, Arefeh Rouhi, Florian Kuchenbauer, Lars Palmqvist
MicroRNA-155 (miR-155) is an oncogenic miRNA upregulated in various tumor types and leukemias and has been suggested as a potential drug target. Based on our previous work detecting high miR-155 levels in response to Meis1 overexpression in a murine Hox leukemia model, we show here the relationship among HOXA9, MEIS1, and miR-155 levels in MLL-translocated acute myeloid leukemia (AML) patients. Using mouse bone marrow cells transformed by MLL-fusion genes expressing graduated levels of Meis1, we show a positive correlation between miR-155 and Meis1...
September 13, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27617578/upregulation-of-flt3-is-a-passive-event-in-hoxa9-meis1-induced-acute-myeloid-leukemia-in-mice
#16
A Staffas, L S Arabanian, S Y Wei, A Jansson, S Ståhlman, P Johansson, L Fogelstrand, J Cammenga, F Kuchenbauer, L Palmqvist
HOXA9, MEIS1 and FLT3 are genes frequently upregulated in human acute myeloid leukemia. Hoxa9 and Meis1 also cooperate to induce aggressive AML with high Flt3 expression in mice, suggesting an important role for Flt3 in Hoxa9/Meis1-induced leukemogenesis. To define the role of Flt3 in AML with high Hoxa9/Meis1, we treated mice with Hoxa9/Meis1-induced AML with the Flt3 inhibitor AC220, used an Flt3-ligand (FL-/-) knockout model, and investigated whether overexpression of Flt3 could induce leukemia together with overexpression of Hoxa9...
March 2017: Oncogene
https://www.readbyqxmd.com/read/27607579/distal-regulation-of-c-myb-expression-during-il-6-induced-differentiation-in-murine-myeloid-progenitor-m1-cells
#17
Junfang Zhang, Bingshe Han, Xiaoxia Li, Juraj Bies, Penglei Jiang, Richard P Koller, Linda Wolff
The c-Myb transcription factor is a major regulator that controls differentiation and proliferation of hematopoietic progenitor cells, which is frequently deregulated in hematological diseases, such as lymphoma and leukemia. Understanding of the mechanisms regulating the transcription of c-myb gene is challenging as it lacks a typical promoter and multiple factors are involved. Our previous studies identified some distal regulatory elements in the upstream regions of c-myb gene in murine myeloid progenitor M1 cells, but the detailed mechanisms still remain unclear...
2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27583552/the-tale-homeodomain-transcription-factor-meis1-activates-the-pro-metastatic-melanoma-cell-adhesion-molecule-mcam-to-promote-migration-of-pancreatic-cancer-cells
#18
Johannes von Burstin, Friedrich Bachhuber, Mariel Paul, Roland M Schmid, Anil K Rustgi
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most deadly types of cancer, and the majority of pancreatic cancer deaths is caused by metastasis. Therapeutic options for systemic disease are limited, in particular due to the heterogeneous events leading to tumor dissemination. Previous studies highlighted an association of the homeodomain transcription factor MEIS1 with a ductal phenotype in pancreatic tissue architecture. Using immunohistochemistry, we demonstrate that MEIS1 is expressed in aberrant duct structures of Ela-TGFα transgenic mice as well as in pancreatic intraepithelial neoplasia (PanINs), primary PDAC, and metastatic disease in Ptf1a(Cre/+) ;LSL-Kras(G12D/+) mice...
March 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27579918/meta-analysis-of-transcriptome-regulation-during-induction-to-cardiac-myocyte-fate-from-mouse-and-human-fibroblasts
#19
Shima Rastegar-Pouyani, Niusha Khazaei, Ping Wee, Moein Yaqubi, Abdulshakour Mohammadnia
Ectopic expression of a defined set of transcription factors (TFs) can directly convert fibroblasts into a cardiac myocyte cell fate. Beside inefficiency in generating induced cardiomyocytes (iCMs), the molecular mechanisms that regulate this process remained to be well defined. The main purpose of this study was to provide better insight on the transcriptome regulation and to introduce a new strategy for candidating TFs for the transdifferentiation process. Eight mouse and three human high quality microarray data sets were analyzed to find differentially expressed genes (DEGs), which we integrated with TF-binding sites and protein-protein interactions to construct gene regulatory and protein-protein interaction networks...
August 31, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27576349/sox1-is-correlated-to-stemness-state-regulator-sall4-through-progression-and-invasiveness-of-esophageal-squamous-cell-carcinoma
#20
Abolfazl Rad, Saeed Esmaeili Dizghandi, Mohammad Reza Abbaszadegan, Negin Taghechian, Maryam Najafi, Mohammad Mahdi Forghanifard
SOX1, as a tumor suppressor, play anti-tumorigenecity role in different cells and its expression is inhibited in a variety of cancers. The aim of this study was to evaluate SOX1 expression and its correlation with cancer stem cell (CSC) markers in ESCC. Using real time PCR, the relative comparative expression of SOX1 in 40 ESCC samples was assessed compared to related margin normal tissues, and its correlation with CSC markers including SALL4, SOX2, and MEIS1 was analyzed statistically. The results revealed significant under-expression of SOX1 in ESCC in significant correlation with different indices of poor prognosis including depth of tumor invasion (P=0...
December 15, 2016: Gene
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