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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
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
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
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
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 Grosveld, Steven Goossens, Jody J Haigh, Danny Huylebroeck
In human 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
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
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
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
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...
September 20, 2016: Oncology Reports
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
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...
2016: BMC Genomics
Jagmohan Singh, Ettickan Boopathi, Sankar Addya, Benjamin Phillips, Isidore Rigoutsos, Raymond B Penn, Satish Rattan
A comprehensive -omic, computational, and physiological approach was employed to examine the (previously unexplored) role of microRNAs (miRNAs) as regulators of IAS smooth muscle contractile phenotype and basal tone. MicroRNA 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 up-regulated in aging IAS...
September 15, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
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
Hila Milo Rasouly, Sudhir Kumar, Stefanie Chan, Anna Pisarek-Horowitz, Richa Sharma, Qiongchao J Xi, Yuriko Nishizaki, Yujiro Higashi, David J Salant, Richard L Maas, Weining Lu
Primary glomerulocystic kidney disease is a special form of renal cystic disorder characterized by Bowman's space dilatation in the absence of tubular cysts. ZEB2 is a SMAD-interacting transcription factor involved in Mowat-Wilson syndrome, a congenital disorder with an increased risk for kidney anomalies. Here we show that deletion of Zeb2 in mesenchyme-derived nephrons with either Pax2-cre or Six2-cre causes primary glomerulocystic kidney disease without tubular cysts in mice. Glomerulotubular junction analysis revealed many atubular glomeruli in the kidneys of Zeb2 knockout mice, which explains the presence of glomerular cysts in the absence of tubular dilatation...
August 30, 2016: Kidney International
Qingping Jiang, Ying Zhou, Huiling Yang, Libo Li, Xiaojie Deng, Chao Cheng, Yingying Xie, Xiaojun Luo, Weiyi Fang, Zhen Liu
miR-203 is a tumor suppressor that is disregulated in numerous malignancies including nasopharyngeal carcinoma (NPC). However, the role of miR-203 in suppressing tumor stemness, chemotherapy resistance as well as its molecular mechanisms are unclear. In this study, we observed that miR-203 suppressed cell migration, invasion, tumor stemness, and chemotherapy resistance to cisplatin (DDP) in vitro and in vivo. miR-203 exerted these effects by targeting ZEB2 and downstream epithelial-mesenchymal transition (EMT) and tumor stemness signals...
August 30, 2016: Oncotarget
Martin H M Sailer, Durga Sarvepalli, Catherine Brégère, Urs Fisch, Marin Guentchev, Michael Weller, Raphael Guzman, Bernhard Bettler, Arkasubhra Ghosh, Gregor Hutter
Epithelial to mesenchymal transition (EMT) describes the process of epithelium transdifferentiating into mesenchyme. EMT is a fundamental process during embryonic development that also commonly occurs in glioblastoma, the most frequent malignant brain tumor. EMT has also been observed in multiple carcinomas outside the brain including breast cancer, lung cancer, colon cancer, gastric cancer. EMT is centrally linked to malignancy by promoting migration, invasion and metastasis formation. The mechanisms of EMT induction are not fully understood...
2016: Journal of Visualized Experiments: JoVE
Hanlu Yin, Yi Wang, Wenping Chen, Shanliang Zhong, Zhian Liu, Jianhua Zhao
High expression of Chemokine receptor 4 (CXCR4) is important in tumor invasion, metastasis, drug-resistance and maintenance of stemness in non-small cell lung cancer (NSCLC). We therefore studied the molecular characteristics of drug-resistant CXCR4-positive cells on epithelial-mesenchymal transition (EMT) for the future identification of the tumor cells with the properties of both EMT and stemness. EMT RT(2) Profier PCR Array was performed to determine the expression levels of mRNA genes in A549 with TGF-β1 induced EMT (A549/TGF-β1) and gefitinib-resistant CXCR4-positive cells (A549/GR)...
December 5, 2016: Gene
Markus Kaller, Heiko Hermeking
The epithelial-mesenchymal-transition (EMT) represents a morphogenetic program involved in developmental processes such as gastrulation and neural crest formation. The EMT program is co-opted by epithelial tumor cells and endows them with features necessary for spreading to distant sites, such as invasion, migration, apoptosis resistance and stemness. Thereby, EMT facilitates metastasis formation and therapy resistance. A growing number of transcription factors has been implicated in the regulation of EMT. These include EMT-inducing transcription factors (EMT-TFs), the most prominent being SNAIL, SLUG, ZEB1, ZEB2 and TWIST, and negative regulators of EMT, such as p53...
2016: Advances in Experimental Medicine and Biology
Horacio Cardenas, Janice Zhao, Edyta Vieth, Kenneth P Nephew, Daniela Matei
Cancer cells acquire essential characteristics for metastatic dissemination through the process of epithelial-to-mesenchymal transition (EMT), which is regulated by gene expression and chromatin remodeling changes. The enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the polycomb repressive complex 2 (PRC2), catalyzes trimethylation of lysine 27 of histone H3 (H3K27me3) to repress gene transcription. Here we report the functional roles of EZH2-catalyzed H3K27me3 during EMT in ovarian cancer (OC) cells...
August 22, 2016: Oncotarget
Patricia T Jimenez, Monica A Mainigi, R Ann Word, W Lee Kraus, Carole R Mendelson
For successful embryo implantation, endometrial stromal cells must undergo functional and morphological changes, referred to as decidualization. However, the molecular mechanisms that regulate implantation and decidualization are not well defined. Here we demonstrate that the estradiol- and progesterone-regulated microRNA (miR)-200 family was markedly down-regulated in mouse endometrial stromal cells prior to implantation, whereas zinc finger E-box binding homeobox-1 and -2 and other known and predicted targets were up-regulated...
September 2016: Molecular Endocrinology
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