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https://www.readbyqxmd.com/read/27904778/long-non-coding-rna-ccat2-promotes-gastric-cancer-proliferation-and-invasion-by-regulating-the-e-cadherin-and-lats2
#1
Yong-Jun Wang, Jian-Zhen Liu, Pei Lv, Yi Dang, Jiang-Yan Gao, Yong Wang
Dysregulation of long non-coding RNAs (lncRNAs) play important roles in tumor development and progression. The long non-coding RNA CCAT2 has been identified to be up-regulated in gastric cancer (GC). However, the detailed molecular mechanism of CCAT2 involved in GC progression is still unknown. The aim of this study was to explore the expression and role of CCAT2 in GC progression. In the study, the expression levels of CCAT2 were significantly up-regulated in 108 cases GC tissues compared with adjacent non-tumor tissues by qRT-PCR analysis...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27861158/myc-associated-zinc-finger-protein-promotes-the-invasion-and-metastasis-of-hepatocellular-carcinoma-by-inducing-epithelial-mesenchymal-transition
#2
Wei Luo, Xiaonian Zhu, Wei Liu, Yuan Ren, Chunhua Bei, Linyuan Qin, Xueyan Miao, Fen Tang, Guifang Tang, Shengkui Tan
MYC associated zinc finger protein (MAZ) plays a key role in regulation of gene expression and tumor development. Studies have shown that deregulated expression of MAZ is closely related to the progression of tumors such as glioblastoma, breast cancer, prostate cancer and liposarcoma. However, the role of MAZ in hepatocellular carcinoma (HCC) has not been fully elucidated. Here, we found that expression of MAZ was increased in HCC and correlated to the distant metastasis of HCC. Moreover, we found that MAZ had a relationship with zinc finger E-box binding homeobox 1 and 2 (ZEB1 and ZEB2), two important mesenchymal markers in epithelial-mesenchymal transition (EMT) that were over-expressed in HCC...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27845906/specific-micro-rna-expression-patterns-distinguish-the-basal-and-luminal-subtypes-of-muscle-invasive-bladder-cancer
#3
Andrea E Ochoa, Woonyoung Choi, Xiaoping Su, Arlene Siefker-Radtke, Bogdan Czerniak, Colin Dinney, David J McConkey
The roles of non-coding RNAs in controlling clinical and biological heterogeneity in bladder cancer remain unclear. We used TCGA's published dataset (n = 405 tumors) as a discovery cohort and created a new validation cohort to define the miRNA expression patterns in the basal and luminal molecular subtypes of muscle-invasive bladder cancer (MIBC). We identified 63 miRNAs by PAM, which optimally identified basal and luminal tumors. The targets of the top luminal miRNAs were activators of EMT (ZEB1, ZEB2) and basal subtype transcription (IL-6, EGFR, STAT3), whereas the targets of the top basal miRNAs were involved in adipogenesis pathways and luminal breast cancer (ERBB2, ERBB3)...
November 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27832070/pleiotropic-associations-of-allelic-variants-in-a-2q22-region-with-risks-of-major-human-diseases-and-mortality
#4
Alexander M Kulminski, Liang He, Irina Culminskaya, Yury Loika, Yelena Kernogitski, Konstantin G Arbeev, Elena Loiko, Liubov Arbeeva, Olivia Bagley, Matt Duan, Arseniy Yashkin, Fang Fang, Mikhail Kovtun, Svetlana V Ukraintseva, Deqing Wu, Anatoliy I Yashin
Gaining insights into genetic predisposition to age-related diseases and lifespan is a challenging task complicated by the elusive role of evolution in these phenotypes. To gain more insights, we combined methods of genome-wide and candidate-gene studies. Genome-wide scan in the Atherosclerosis Risk in Communities (ARIC) Study (N = 9,573) was used to pre-select promising loci. Candidate-gene methods were used to comprehensively analyze associations of novel uncommon variants in Caucasians (minor allele frequency~2...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27831545/neuroimaging-findings-in-mowat-wilson-syndrome-a-study-of-54-patients
#5
Livia Garavelli, Ivan Ivanovski, Stefano Giuseppe Caraffi, Daniela Santodirocco, Marzia Pollazzon, Duccio Maria Cordelli, Ebtesam Abdalla, Patrizia Accorsi, Margaret P Adam, Chiara Baldo, Allan Bayat, Elga Belligni, Federico Bonvicini, Jeroen Breckpot, Bert Callewaert, Guido Cocchi, Goran Cuturilo, Koenraad Devriendt, Mary Beth Dinulos, Olivera Djuric, Roberta Epifanio, Francesca Faravelli, Debora Formisano, Lucio Giordano, Marina Grasso, Sabine Grønborg, Alessandro Iodice, Lorenzo Iughetti, Didier Lacombe, Massimo Maggi, Baris Malbora, Isabella Mammi, Sebastien Moutton, Rikke Møller, Petra Muschke, Manuela Napoli, Chiara Pantaleoni, Rosario Pascarella, Alessandro Pellicciari, Maria Luisa Poch-Olive, Federico Raviglione, Francesca Rivieri, Carmela Russo, Salvatore Savasta, Gioacchino Scarano, Angelo Selicorni, Margherita Silengo, Giovanni Sorge, Luigi Tarani, Luis Gonzaga Tone, Annick Toutain, Aurelien Trimouille, Elvis Terci Valera, Samantha Schrier Vergano, Nicoletta Zanotta, Marcella Zollino, William B Dobyns, Alex R Paciorkowski
PURPOSE: Mowat-Wilson syndrome (MWS) is a genetic disease characterized by distinctive facial features, moderate to severe intellectual disability, and congenital malformations, including Hirschsprung disease, genital and eye anomalies, and congenital heart defects, caused by haploinsufficiency of the ZEB2 gene. To date, no characteristic pattern of brain dysmorphology in MWS has been defined. METHODS: Through brain magnetic resonance imaging (MRI) analysis, we delineated a neuroimaging phenotype in 54 MWS patients with a proven ZEB2 defect, compared it with the features identified in a thorough review of published cases, and evaluated genotype-phenotype correlations...
November 10, 2016: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/27799067/identification-of-a-rai1-associated-disease-network-through-integration-of-exome-sequencing-transcriptomics-and-3d-genomics
#6
Maria Nicla Loviglio, Christine R Beck, Janson J White, Marion Leleu, Tamar Harel, Nicolas Guex, Anne Niknejad, Weimin Bi, Edward S Chen, Isaac Crespo, Jiong Yan, Wu-Lin Charng, Shen Gu, Ping Fang, Zeynep Coban-Akdemir, Chad A Shaw, Shalini N Jhangiani, Donna M Muzny, Richard A Gibbs, Jacques Rougemont, Ioannis Xenarios, James R Lupski, Alexandre Reymond
BACKGROUND: Smith-Magenis syndrome (SMS) is a developmental disability/multiple congenital anomaly disorder resulting from haploinsufficiency of RAI1. It is characterized by distinctive facial features, brachydactyly, sleep disturbances, and stereotypic behaviors. METHODS: We investigated a cohort of 15 individuals with a clinical suspicion of SMS who showed neither deletion in the SMS critical region nor damaging variants in RAI1 using whole exome sequencing. A combination of network analysis (co-expression and biomedical text mining), transcriptomics, and circularized chromatin conformation capture (4C-seq) was applied to verify whether modified genes are part of the same disease network as known SMS-causing genes...
November 1, 2016: Genome Medicine
https://www.readbyqxmd.com/read/27785072/mir-144-functions-as-a-tumor-suppressor-in-breast-cancer-through-inhibiting-zeb1-2-mediated-epithelial-mesenchymal-transition-process
#7
Yuliang Pan, Jun Zhang, Huiqun Fu, Liangfang Shen
Breast cancer is the most common cancer in women worldwide. Local invasion, metastasis, and chemotherapy resistance are the obstacles for treatment of breast cancer. In this study, we aim to investigate the role of miR-144 in breast cancer. We demonstrate that the expression of miR-144 is downregulated in breast cancer and cell lines, and lower miR-144 expression is associated with poor differentiation, higher clinical stage, and lymph node metastasis in patients with breast cancer. The rescue of miR-144 expression is able to inhibit the cell proliferation and the ability of cell migration and invasion...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27767083/mir-200-family-controls-late-steps-of-postnatal-forebrain-neurogenesis-via-zeb2-inhibition
#8
Christophe Beclin, Philipp Follert, Elke Stappers, Serena Barral, Coré Nathalie, Antoine de Chevigny, Virginie Magnone, Kévin Lebrigand, Ute Bissels, Danny Huylebroeck, Andreas Bosio, Pascal Barbry, Eve Seuntjens, Harold Cremer
During neurogenesis, generation, migration and integration of the correct numbers of each neuron sub-type depends on complex molecular interactions in space and time. MicroRNAs represent a key control level allowing the flexibility and stability needed for this process. Insight into the role of this regulatory pathway in the brain is still limited. We performed a sequential experimental approach using postnatal olfactory bulb neurogenesis in mice, starting from global expression analyses to the investigation of functional interactions between defined microRNAs and their targets...
October 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27761656/hoxb8-promotes-tumor-metastasis-and-the-epithelial-mesenchymal-transition-via-zeb2-targets-in-gastric-cancer
#9
Wen-Jin Ding, Min Zhou, Mei-Mei Chen, Chun-Ying Qu
PURPOSE: The homeobox B8 (HOXB8) functions as a sequence-specific transcription factor that is involved in development. Increased expression of this gene is associated with a wide variety of tumor; however, its function in gastric cancer has not been clarified. In the present study, the expression of HOXB8 in gastric cancer tissues and influence of HOXB8 on gastric cancer cellular were evaluated. METHODS: The expression levels of HOXB8 mRNA in human gastric cancer tissues were analyzed through quantitative RT-PCR...
October 19, 2016: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/27756750/the-emt-regulator-zeb2-is-a-novel-dependency-of-human-and-murine-acute-myeloid-leukemia
#10
Hubo Li, Brenton G Mar, Huadi Zhang, Rishi V Puram, Francisca Vazquez, Barbara A Weir, William C Hahn, Benjamin Ebert, David Pellman
Acute myeloid leukemia (AML) is a heterogeneous disease with complex molecular pathophysiology. To systematically characterize AML's genetic dependencies, we conducted genome-scale shRNA screens in 17 AML cell lines and analyzed dependencies relative to parallel screens in 199 cell lines of other cancer types. We identified 353 genes specifically required for AML cell proliferation. To validate the in vivo relevance of genetic dependencies observed in human cell lines, we performed a secondary screen in a syngeneic murine AML model driven by the MLL-AF9 oncogenic fusion protein...
October 18, 2016: Blood
https://www.readbyqxmd.com/read/27748842/downregulation-of-zeb2-as1-decreased-tumor-growth-and-metastasis-in-hepatocellular-carcinoma
#11
Tian Lan, Lei Chang, Long Wu, Yufeng Yuan
Hepatocellular carcinoma (HCC) remains one of the most common types of cancer worldwide and prognosis remains poor. Previous studies have suggested that long non‑coding RNAs (lncRNAs) may be key regulators of tumor development and progression in HCC. It has been determined that 61‑72% of transcribed regions contain lncRNAs in the antisense orientation (aslncRNAs). However, the function of aslncRNAs in HCC remains to be elucidated. The present study investigated the function of the aslncRNA zinc finger E‑box binding homeobox 2 antisense RNA 1 (ZEB2‑AS1) in 40 HCC tissues and 5 different human HCC cell lines using reverse transcription‑quantitative polymerase chain reaction...
November 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27739137/zeb2-regulates-cell-fate-at-the-exit-from-epiblast-state-in-mouse-embryonic-stem-cells
#12
Agata Stryjewska, Ruben Dries, Tim Pieters, Griet Verstappen, Andrea Conidi, Kathleen Coddens, Annick Francis, Lieve Umans, Wilfred F J Van IJcken, Geert Berx, Leo A van Grunsven, Frank G Grosveld, Steven Goossens, Jody J Haigh, Danny Huylebroeck
In human embryonic stem cells (ESCs) the transcription factor Zeb2 regulates neuroectoderm versus mesendoderm formation, but it is unclear how Zeb2 affects the global transcriptional regulatory network in these cell-fate decisions. We generated Zeb2 knockout (KO) mouse ESCs, subjected them as embryoid bodies (EBs) to neural and general differentiation and carried out temporal RNA-sequencing (RNA-seq) and reduced representation bisulfite sequencing (RRBS) analysis in neural differentiation. This shows that Zeb2 acts preferentially as a transcriptional repressor associated with developmental progression and that Zeb2 KO ESCs can exit from their naïve state...
October 14, 2016: Stem Cells
https://www.readbyqxmd.com/read/27733346/direct-interaction-between-mir-203-and-zeb2-suppresses-epithelial-mesenchymal-transition-signaling-and-reduces-lung-adenocarcinoma-chemoresistance
#13
Xunhuang Duan, Zhaojian Fu, Lingyuan Gao, Jin Zhou, Xiaojie Deng, Xiaojun Luo, Weiyi Fang, Rongcheng Luo
miR-203 is a tumor suppressor which participates in the pathogenesis of many tumors including lung adenocarcinoma. However, the role of miR-203 in suppressing chemotherapy resistance to cisplatin (cis-diamminedichloroplatinum; DDP) as well as its molecular mechanism is still to be determined in lung adenocarcinoma. In this study, we found that miR-203 decreased lung cancer cell migration and invasion, and that increased miR-203 expression sensitized lung adenocarcinoma cells to DDP in vitro Furthermore, ZEB2 was found to be a direct target of miR-203, which induces epithelial-mesenchymal transition (EMT) signal...
October 12, 2016: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/27719642/bona-fide-targets-of-deregulated-micrornas-in-non-small-cell-lung-cancer-as-tool-to-identify-novel-therapeutic-targets-a-review
#14
Monica Cipollini, Stefano Landi, Federica Gemignani
BACKGROUND: Non-small-cell lung cancer (NSCLC) is an aggressive neoplasm with a poor survival and novel therapies are urgently needed. The study of deregulated micro-RNAs (dereg-miRs) could constitute a strategy helping to detect specific genes playing a relevant role in the disease. Thus, the oncoproteins encoded by these genes could be exploited as novel therapeutic targets to be inhibited by small molecules, aptamers, or monoclonal antibodies. METHODS: The present review is focused on candidate genes having convincing biological evidences to be both bona fide targets for dereg-miRs and playing a role in NSCLC progression...
October 6, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27683414/the-emt-transcription-factor-zeb2-controls-adult-murine-hematopoietic-differentiation-by-regulating-cytokine-signaling
#15
Jin Li, Tamara Riedt, Steven Goossens, Carmen Carrillo García, Sabrina Szczepanski, Maria Brandes, Tim Pieters, Linne Dobrosch, Ines Gütgemann, Natalie Farla, Enrico Radaelli, Paco Hulpiau, Nikhil Mallela, Holger Fröhlich, Roberta La Starza, Caterina Matteucci, Tong Chen, Peter Brossart, Cristina Mecucci, Danny Huylebroeck, Jody J Haigh, Viktor Janzen
Epithelial-to-mesenchymal-transition (EMT) is critical for normal embryogenesis and effective post-natal wound healing, but is also associated with cancer metastasis. SNAIL, ZEB and TWIST families of transcription factors are key modulators of the EMT process, but their precise roles in adult hematopoietic development and homeostasis remain unclear. Here we report that genetic inactivation of Zeb2 results in increased frequency of stem and progenitor subpopulations within the bone marrow (BM) and spleen and that these changes accompany differentiation defects in multiple hematopoietic cell lineages...
September 28, 2016: Blood
https://www.readbyqxmd.com/read/27666412/colorectal-cancer-cell-derived-microrna200-modulates-the-resistance-of-adjacent-blood-endothelial-barriers-in%C3%A2-vitro
#16
Silvio Holzner, Daniel Senfter, Serena Stadler, Anna Staribacher, Chi Huu Nguyen, Anna Gaggl, Silvana Geleff, Nicole Huttary, Sigurd Krieger, Walter Jäger, Helmut Dolznig, Robert M Mader, Georg Krupitza
Since cancer cells, when grown as spheroids, display drug sensitivity and radiation resistance patterns such as seen in vivo we recently established a three‑dimensional (3D) in vitro model recapitulating colorectal cancer (CRC)-triggered lymphatic endothelial cell (LEC)‑barrier breaching to study mechanisms of intra‑/extravasation. CRC metastasizes not only through lymphatics but also through blood vessels and here we extend the 3D model to the interaction of blood endothelial cells (BECs) with naïve and 5‑fluorouracil (5‑FU)‑resistant CRC CCL227 cells...
November 2016: Oncology Reports
https://www.readbyqxmd.com/read/27659015/dnmt1-regulates-epithelial-mesenchymal-transition-and-cancer-stem-cells-which-promotes-prostate-cancer-metastasis
#17
Eunsohl Lee, Jingcheng Wang, Kenji Yumoto, Younghun Jung, Frank C Cackowski, Ann M Decker, Yan Li, Renny T Franceschi, Kenneth J Pienta, Russell S Taichman
Cancer metastasis is a multistep process associated with the induction of an epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs). Although significant progress has been made in understanding the molecular mechanisms regulating EMT and the CSC phenotype, little is known of how these processes are regulated by epigenetics. Here we demonstrate that reduced expression of DNA methyltransferase 1 (DNMT1) plays an important role in the induction of EMT and the CSC phenotype by prostate cancer (PCa) cells, with enhanced tumorigenesis and metastasis...
September 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27640124/non-linear-interactions-between-candidate-genes-of-myocardial-infarction-revealed-in-mrna-expression-profiles
#18
Katherine Hartmann, Michał Seweryn, Samuel K Handleman, Grzegorz A Rempała, Wolfgang Sadee
BACKGROUND: Alterations in gene expression are key events in disease etiology and risk. Poor reproducibility in detecting differentially expressed genes across studies suggests individual genes may not be sufficiently informative for complex diseases, such as myocardial infarction (MI). Rather, dysregulation of the 'molecular network' may be critical for pathogenic processes. Such a dynamic network can be built from pairwise non-linear interactions. RESULTS: We investigate non-linear interactions represented in mRNA expression profiles that integrate genetic background and environmental factors...
September 17, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27634012/aging-associated-changes-in-microrna-expression-profile-of-internal-anal-sphincter-smooth-muscle-role-of-microrna-133a
#19
Jagmohan Singh, Ettickan Boopathi, Sankar Addya, Benjamin Phillips, Isidore Rigoutsos, Raymond B Penn, Satish Rattan
A comprehensive genomic and proteomic, computational, and physiological approach was employed to examine the (previously unexplored) role of microRNAs (miRNAs) as regulators of internal anal sphincter (IAS) smooth muscle contractile phenotype and basal tone. miRNA profiling, genome-wide expression, validation, and network analyses were employed to assess changes in mRNA and miRNA expression in IAS smooth muscles from young vs. aging rats. Multiple miRNAs, including rno-miR-1, rno-miR-340-5p, rno-miR-185, rno-miR-199a-3p, rno-miR-200c, rno-miR-200b, rno-miR-31, rno-miR-133a, and rno-miR-206, were found to be upregulated in aging IAS...
November 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27629361/microrna-expression-profiling-and-functional-annotation-analysis-of-their-targets-modulated-by-oxidative-stress-during-embryonic-heart-development-in-diabetic-mice
#20
Daoyin Dong, Yuji Zhang, E Albert Reece, Lei Wang, Christopher R Harman, Peixin Yang
Maternal pregestational diabetes mellitus (PGDM) induces congenital heart defects (CHDs). The molecular mechanism underlying PGDM-induced CHDs is unknown. microRNAs (miRNAs), small non-coding RNAs, repress gene expression at the posttranscriptional level and play important roles in heart development. We performed a global miRNA profiling study to assist in revealing potential miRNAs modulated by PGDM and possible developmental pathways regulated by miRNAs during heart development. A total of 149 mapped miRNAs in the developing heart were significantly altered by PGDM...
October 2016: Reproductive Toxicology
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