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https://www.readbyqxmd.com/read/28345455/recurrent-epigenetic-silencing-of-the-ptprd-tumor-suppressor-in-laryngeal-squamous-cell-carcinoma
#1
Marcin Szaumkessel, Sonia Wojciechowska, Joanna Janiszewska, Natalia Zemke, Ewa Byzia, Katarzyna Kiwerska, Magdalena Kostrzewska-Poczekaj, Adam Ustaszewski, Malgorzata Jarmuz-Szymczak, Reidar Grenman, Malgorzata Wierzbicka, Anna Bartochowska, Krzysztof Szyfter, Maciej Giefing
Cellular processes like differentiation, mitotic cycle, and cell growth are regulated by tyrosine kinases with known oncogenic potential and tyrosine phosphatases that downmodulate the first. Therefore, tyrosine phosphatases are recurrent targets of gene alterations in human carcinomas. We and others suggested recently a tumor suppressor function of the PTPRD tyrosine phosphatase and reported homozygous deletions of the PTPRD locus in laryngeal squamous cell carcinoma. In this study, we investigated other gene-inactivating mechanisms potentially targeting PTPRD, including loss-of-function mutations and also epigenetic alterations like promoter DNA hypermethylation...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28335020/znhit3-is-defective-in-peho-syndrome-a-severe-encephalopathy-with-cerebellar-granule-neuron-loss
#2
Anna-Kaisa Anttonen, Anni Laari, Maria Kousi, Yawei J Yang, Tiina Jääskeläinen, Mirja Somer, Eija Siintola, Eveliina Jakkula, Mikko Muona, Saara Tegelberg, Tuula Lönnqvist, Helena Pihko, Leena Valanne, Anders Paetau, Melody P Lun, Johanna Hästbacka, Outi Kopra, Tarja Joensuu, Nicholas Katsanis, Maria K Lehtinen, Jorma J Palvimo, Anna-Elina Lehesjoki
Progressive encephalopathy with oedema, hypsarrhythmia, and optic atrophy (PEHO) syndrome is an early childhood onset, severe autosomal recessive encephalopathy characterized by extreme cerebellar atrophy due to almost total granule neuron loss. By combining homozygosity mapping in Finnish families with Sanger sequencing of positional candidate genes and with exome sequencing a homozygous missense substitution of leucine for serine at codon 31 in ZNHIT3 was identified as the primary cause of PEHO syndrome. ZNHIT3 encodes a nuclear zinc finger protein previously implicated in transcriptional regulation and in small nucleolar ribonucleoprotein particle assembly and thus possibly to pre-ribosomal RNA processing...
March 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334365/effect-of-kit-and-pdgfra-mutations-on-survival-in-patients-with-gastrointestinal-stromal-tumors-treated-with-adjuvant-imatinib-an-exploratory-analysis-of-a-randomized-clinical-trial
#3
Heikki Joensuu, Eva Wardelmann, Harri Sihto, Mikael Eriksson, Kirsten Sundby Hall, Annette Reichardt, Jörg T Hartmann, Daniel Pink, Silke Cameron, Peter Hohenberger, Salah-Eddin Al-Batran, Marcus Schlemmer, Sebastian Bauer, Bengt Nilsson, Raija Kallio, Jouni Junnila, Aki Vehtari, Peter Reichardt
Importance: Little is known about whether the duration of adjuvant imatinib influences the prognostic significance of KIT proto-oncogene receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor α (PDGFRA) mutations. Objective: To investigate the effect of KIT and PDGFRA mutations on recurrence-free survival (RFS) in patients with gastrointestinal stromal tumors (GISTs) treated with surgery and adjuvant imatinib. Design, Setting, and Participants: This exploratory study is based on the Scandinavian Sarcoma Group VIII/Arbeitsgemeinschaft Internistische Onkologie (SSGXVIII/AIO) multicenter clinical trial...
March 23, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28329758/lactb-is-a-tumour-suppressor-that-modulates-lipid-metabolism-and-cell-state
#4
Zuzana Keckesova, Joana Liu Donaher, Jasmine De Cock, Elizaveta Freinkman, Susanne Lingrell, Daniel A Bachovchin, Brian Bierie, Verena Tischler, Aurelia Noske, Marian C Okondo, Ferenc Reinhardt, Prathapan Thiru, Todd R Golub, Jean E Vance, Robert A Weinberg
Post-mitotic, differentiated cells exhibit a variety of characteristics that contrast with those of actively growing neoplastic cells, such as the expression of cell-cycle inhibitors and differentiation factors. We hypothesized that the gene expression profiles of these differentiated cells could reveal the identities of genes that may function as tumour suppressors. Here we show, using in vitro and in vivo studies in mice and humans, that the mitochondrial protein LACTB potently inhibits the proliferation of breast cancer cells...
March 22, 2017: Nature
https://www.readbyqxmd.com/read/28322595/improving-the-quality-of-aav-vector-preparations-the-challenge-of-product-related-impurities
#5
Maria Schnödt, Hildegard Büning
Adeno-associated viral (AAV) vectors have emerged as one of the most popular gene transfer systems in both, research and clinical gene therapy. As AAV vectors are derived from a stealth, nonpathogenic virus and lack an active integrase activity, vectors are frequently applied for in vivo gene therapy of liver, muscle and other post-mitotic tissues. While long-term transgene expression from AAV vector episomes is reported from these tissues, AAV's episomal nature - once regarded as disadvantage - has become an attractive feature for gene editing approaches targeting proliferating cells...
March 21, 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28320919/pan-cancer-analysis-distinguishes-transcriptional-changes-of-aneuploidy-from-proliferation
#6
Christopher Buccitelli, Lorena Salgueiro, Konstantina Rowald, Rocio Sotillo, Balca R Mardin, Jan O Korbel
Patterns of gene expression in tumors can arise as a consequence of or result in genomic instability, characterized by the accumulation of somatic copy number alterations (SCNAs) and point mutations (PMs). Expression signatures have been widely used as markers for genomic instability, and both SCNAs and PMs could be thought to associate with distinct signatures given their different formation mechanisms. Here we test this notion by systematically investigating SCNA, PM, and transcriptome data from 2660 cancer patients representing 11 tumor types...
March 20, 2017: Genome Research
https://www.readbyqxmd.com/read/28319828/genistein-affects-proliferation-and-migration-of-bovine-oviductal-epithelial-cells
#7
Daniela C García, Pablo A Valdecantos, Dora C Miceli, Mariela Roldán-Olarte
Genistein is one of the most abundant isoflavones in soybean. This molecule induces cell cycle arrest and apoptosis in different normal and cancer cells. Genistein has been of considerable interest due to its adverse effects on bovine reproduction, altering estrous cycle, implantation and fetal development and producing subfertility or infertility. The objective of this work was to study the effects of genistein on the expression of selected genes involved in the regulation of cell cycle and apoptosis. Primary cultures of bovine oviductal epithelial cells (BOEC) were treated with different genistein concentrations (0...
March 8, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28302908/tubulin-isotype-substitution-revealed-that-isotype-composition-modulates-microtubule-dynamics-in-c-elegans-embryos
#8
Yu Honda, Kenta Tsuchiya, Eisuke Sumiyoshi, Nami Haruta, Asako Sugimoto
Microtubules (MTs) are polymers composed of α- and β-tubulin heterodimers, which are generally encoded by multiple gene loci. Despite implications of distinct properties of isotypes, how they contribute to diverse MT dynamics in vivo remains unclear. Here, using genome editing and RNAi depletion of tubulin isotypes, we demonstrate that four tubulin isotypes (hereafter α1, α2, β1 and β2) cooperatively confer distinct MT properties in Caenorhabditis elegans early embryos. GFP insertion into each isotype locus reveals their distinct expression levels and MT incorporation rates...
March 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28300657/expression-patterns-of-prune2-is-regulated-by-notch-and-retinoic-acid-signaling-pathways-in-the-zebrafish-embryogenesis
#9
Mrudhula Anuppalle, Sateesh Maddirevula, Ajeet Kumar, Tae-Lin Huh, Joonho Choe, Myungchull Rhee
PRUNE2 has been identified as a susceptible gene for Alzheimer's disease and a marker for leiomyosarcomas. Isoforms of Prune2 regulate neuronal cell differentiation and synaptogenesis. Although expression pattern of Prune2 has been reported in the murine brain, its expression patterns and regulation along vertebrate embryogenesis remain to be further investigated. We thus defined the expression profiles and transcriptional regulation of prune2 in zebrafish embryos. prune2 exhibits maternal expression, but is increased in later embryonic stages, and expressed in the telencephalon, epiphysis cluster, nucleus of the tract of the post optic commissure, spinal cord, cerebellum, tegmentum, anterior lateral line ganglion, posterior lateral line ganglion and rhombomeres 2 through 5...
March 11, 2017: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/28299790/tc-mps1-12-a-novel-mps1-inhibitor-suppresses-a-growth-of-hepatocellular-carcinoma-cells-via-accumulated-chromosomal-instability
#10
Minji Choi, Yoo Hong Min, Jaehyuk Pyo, Chang-Woo Lee, Chang-Young Jang, Ja-Eun Kim
BACKGROUND AND PURPOSE: Chromosomal instability is not only a hallmark of cancer, but also an attractive therapeutic target. A diverse set of mitotic kinases maintains chromosomal stability. One of these is monopolar spindle 1 (Mps1), which is essential for chromosome alignment and for the spindle assembly checkpoint (SAC). Pharmacological inhibition of Mps1 has been suggested as a cancer therapeutic; however, despite the existence of a novel Mps1 inhibitor, TC Mps1 12, no such studies have been performed...
March 15, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28299653/mitotic-gene-bookmarking-an-epigenetic-mechanism-for-coordination-of-lineage-commitment-cell-identity-and-cell-growth
#11
Sayyed K Zaidi, Jane B Lian, Andre van Wijnen, Janet L Stein, Gary S Stein
Epigenetic control of gene expression contributes to dynamic responsiveness of cellular processes that include cell cycle, cell growth and differentiation. Mitotic gene bookmarking, retention of sequence-specific transcription factors at target gene loci, including the RUNX regulatory proteins, provide a novel dimension to epigenetic regulation that sustains cellular identity in progeny cells following cell division. Runx transcription factor retention during mitosis coordinates physiological control of cell growth and differentiation in a broad spectrum of biological conditions, and is associated with compromised gene expression in pathologies that include cancer...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28299429/anther-preferential-expressing-gene-pmr-is-essential-for-the-mitosis-of-pollen-development-in-rice
#12
Yaqin Liu, Ya Xu, Sheng Ling, Shasha Liu, Jialing Yao
Phenotype identification, expression examination, and function prediction declared that the anther-preferential expressing gene PMR may participate in regulation of male gametophyte development in rice. Male germline development in flowering plants produces the pair of sperm cells for double fertilization and the pollen mitosis is a key process of it. Although the structural features of male gametophyte have been defined, the molecular mechanisms regulating the mitotic cell cycle are not well elucidated in rice...
March 15, 2017: Plant Cell Reports
https://www.readbyqxmd.com/read/28297665/mitotic-phosphorylation-of-trex1-c-terminus-disrupts-trex1-regulation-of-the-oligosaccharyltransferase-complex
#13
Martin Kucej, Charles S Fermaintt, Kun Yang, Ricardo A Irizarry-Caro, Nan Yan
TREX1 mutations are associated with several autoimmune and inflammatory diseases. The N-terminal DNase domain of TREX1 is important for preventing self-DNA from activating the interferon response. The C terminus of TREX1 is required for ER localization and regulation of oligosacchariyltransferase (OST) activity. Here, we show that during mitosis TREX1 is predominately phosphorylated at the C-terminal Serine-261 by Cyclin B/CDK1. TREX1 is dephosphorylated quickly at mitotic exit, likely by PP1/PP2-type serine/threonine phosphatase...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28289076/fumarate-mediates-a-chronic-proliferative-signal-in-fumarate-hydratase-inactivated-cancer-cells-by-increasing-transcription-and-translation-of-ferritin-genes
#14
Michael John Kerins, Ajay Vashisht, Benjamin Xi-Tong Liang, Spencer Jordan Duckworth, Brandon John Praslicka, James Akira Wohlschlegel, Aikseng Ooi
Germline mutations of the gene encoding the tricarboxylic acid cycle (TCA cycle) enzyme, fumarate hydratase (FH), cause a hereditary cancer syndrome known as hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC associated tumors harbor biallelic FH inactivation that results in the accumulation of the TCA cycle metabolite, fumarate. Although it is known that the fumarate accumulation can alter cellular signaling, if and how fumarate confers a growth advantage remains unclear. Here we show that fumarate accumulation confers a chronic proliferative signal by disrupting cellular iron signaling...
March 13, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28287327/mechanism-of-cell-intrinsic-adaptation-to-adams-oliver-syndrome-gene-dock6-disruption-highlights-ubiquitin-like-modifier-isg15-as-a-regulator-of-rho-gtpases
#15
Berati Cerikan, Elmar Schiebel
DOCK6 is a RAC1/CDC42 guanine nucleotide exchange factor, however, little is known about its function and sub-cellular localization. DOCK6 regulates the balance between RAC1 and RHOA activity during cell adhesion and is important for CDC42-dependent mitotic chromosome alignment. Surprisingly, a cell intrinsic adaptation mechanism compensates for errors in these DOCK6 functions that arise as a consequence of prolonged DOCK6 depletion or complete removal in DOCK6 knockout cells. Down-regulation of the ubiquitin-like modifier ISG15 accounts for this adaptation...
February 23, 2017: Small GTPases
https://www.readbyqxmd.com/read/28285642/a-new-hope-for-obesity-management-boron-inhibits-adipogenesis-in-progenitor-cells-through-the-wnt-%C3%AE-catenin-pathway
#16
Ayşegül Doğan, Selami Demirci, Hüseyin Apdik, Omer Faruk Bayrak, Sukru Gulluoglu, Emre Can Tuysuz, Oleg Gusev, Albert A Rizvanov, Emrah Nikerel, Fikrettin Şahin
Obesity is a worldwide medical problem resulting in serious morbidity and mortality involving differentiation of pre-adipocytes into mature adipocytes (adipogenesis). Boron treatment has been reported to be associated with weight reduction in experimental animals; however, its effects on pre-adipocyte differentiation and anti-adipogenic molecular mechanisms are unknown. In this study, we demonstrate the inhibitory activities of boric acid (BA) and sodium pentaborate pentahydrate (NaB) on adipogenesis using common cellular models...
April 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28278055/comparative-analyses-identify-molecular-signature-of-mri-classified-svz-associated-glioblastoma
#17
Chin-Hsing Annie Lin, Christopher T Rhodes, ChenWei Lin, Joanna J Phillips, Mitchel S Berger
Glioblastoma (GBM) is a highly aggressive brain cancer with limited therapeutic options. While efforts to identify genes responsible for GBM have revealed mutations and aberrant gene expression associated with distinct types of GBM, patients with GBM are often diagnosed and classified based on MRI features. Therefore, we seek to identify molecular representatives in parallel with MRI classification for group I and group II primary GBM associated with the subventricular zone (SVZ). As group I and II GBM contain stem-like signature, we compared gene expression profiles between these 2 groups of primary GBM and endogenous neural stem progenitor cells to reveal dysregulation of cell cycle, chromatin status, cellular morphogenesis, and signaling pathways in these 2 types of MRI-classified GBM...
February 22, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28272508/amplified-centrosomes-and-mitotic-index-display-poor-concordance-between-patient-tumors-and-cultured-cancer-cells
#18
Karuna Mittal, Da Hoon Choi, Angela Ogden, Shashi Donthamsetty, Brian D Melton, Meenakshi V Gupta, Vaishali Pannu, Guilherme Cantuaria, Sooryanarayana Varambally, Michelle D Reid, Kristin Jonsdottir, Emiel A M Janssen, Mohammad A Aleskandarany, Ian O Ellis, Emad A Rakha, Padmashree C G Rida, Ritu Aneja
Centrosome aberrations (CA) and abnormal mitoses are considered beacons of malignancy. Cancer cell doubling times in patient tumors are longer than in cultures, but differences in CA between tumors and cultured cells are uncharacterized. We compare mitoses and CA in patient tumors, xenografts, and tumor cell lines. We find that mitoses are rare in patient tumors compared with xenografts and cell lines. Contrastingly, CA is more extensive in patient tumors and xenografts (~35-50% cells) than cell lines (~5-15%), although CA declines in patient-derived tumor cells over time...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28270570/baf53b-a-neuron-specific-nucleosome-remodeling-factor-is-induced-after-learning-and-facilitates-long-term-memory-consolidation
#19
Miran Yoo, Kwang-Yeon Choi, Jieun Kim, Mujun Kim, Jaehoon Shim, Jun-Hyeok Choi, Hye-Yeon Cho, Jungpyo Oh, Hyung-Su Kim, Bong-Kiun Kaang, Jin-Hee Han
Although epigenetic mechanisms of gene expression regulation have recently been implicated in memory consolidation and persistence, the role of nucleosome-remodeling is largely unexplored. Recent studies show that the functional loss of BAF53b, a post-mitotic neuron-specific subunit of the BAF nucleosome-remodeling complex, results in the deficit of consolidation of hippocampus-dependent memory and cocaine-associated memory in the rodent brain. However, it is unclear whether BAF53b expression is regulated during memory formation and how BAF53b regulates fear memory in the amygdala, a key brain site for fear memory encoding and storage...
March 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28265828/liver-regeneration-is-impaired-in-mice-with-acute-exposure-to-a-very-low-carbohydrate-diet
#20
Hao Chen, Yandie Lin, Wu Sun, Yun Cai, Hao Li
BACKGROUND: The metabolic response to hepatic insufficiency has been implicated in the regulators of normal liver regeneration. Modulation of nutritional factors has been demonstrated to affect liver regeneration. Diets containing very low carbohydrate and high fat levels cause a unique metabolic state, the effect of which on liver regeneration is unknown. METHODS: Mice were placed on standard mice chow (ND) or a very low carbohydrate diet (VLCD) after 70% partial hepatectomy (PH)...
March 6, 2017: Digestive Diseases and Sciences
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