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Micrornas, Small Gene Regulators with High Therapeutic Promise in Oncology

Christophe F Grosset
2019 Gastroenterology Medicine & Research  
Following the first description in 2002 of the deregulation of miR-15 and miR-16 in Copyright © : Christophe F Grosset MicroRNAs, cancer and therapy GMR.000565. 3(3).2019 chronic myeloid leukemia  ...  DOI: 10.31031/GMR.2019.03.000565 Copyright@ Christophe F Grosset, This article is distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits unrestricted use  ... 
doi:10.31031/gmr.2019.03.000565 fatcat:fbxtoiyrczh75bl5m2jfgp3z2i

SimBA: A methodology and tools for evaluating the performance of RNA-Seq bioinformatic pipelines

Jérôme Audoux, Mikaël Salson, Christophe F. Grosset, Sacha Beaumeunier, Jean-Marc Holder, Thérèse Commes, Nicolas Philippe
2017 BMC Bioinformatics  
The evolution of next-generation sequencing (NGS) technologies has led to increased focus on RNA-Seq. Many bioinformatic tools have been developed for RNA-Seq analysis, each with unique performance characteristics and configuration parameters. Users face an increasingly complex task in understanding which bioinformatic tools are best for their specific needs and how they should be configured. In order to provide some answers to these questions, we investigate the performance of leading
more » ... atic tools designed for RNA-Seq analysis and propose a methodology for systematic evaluation and comparison of performance to help users make well informed choices. Results: To evaluate RNA-Seq pipelines, we developed a suite of two benchmarking tools. SimCT generates simulated datasets that get as close as possible to specific real biological conditions accompanied by the list of genomic incidents and mutations that have been inserted. BenchCT then compares the output of any bioinformatics pipeline that has been run against a SimCT dataset with the simulated genomic and transcriptional variations it contains to give an accurate performance evaluation in addressing specific biological question. We used these tools to simulate a real-world genomic medicine question s involving the comparison of healthy and cancerous cells. Results revealed that performance in addressing a particular biological context varied significantly depending on the choice of tools and settings used. We also found that by combining the output of certain pipelines, substantial performance improvements could be achieved. Conclusion: Our research emphasizes the importance of selecting and configuring bioinformatic tools for the specific biological question being investigated to obtain optimal results. Pipeline designers, developers and users should include benchmarking in the context of their biological question as part of their design and quality control process. Our SimBA suite of benchmarking tools provides a reliable basis for comparing the performance of RNA-Seq bioinformatics pipelines in addressing a specific biological question. We would like to see the creation of a reference corpus of data-sets that would allow accurate comparison between benchmarks performed by different groups and the publication of more benchmarks based on this public corpus. SimBA software and data-set are available at http://
doi:10.1186/s12859-017-1831-5 pmid:28969586 pmcid:PMC5623974 fatcat:5c3im544sne5rmxafoz4ozkpoa

New tumor suppressor microRNAs target glypican-3 in human liver cancer

Flora Cartier, Emilie Indersie, Sarah Lesjean, Justine Charpentier, Katarzyna B. Hooks, Amani Ghousein, Angélique Desplat, Nathalie Dugot-Senant, Véronique Trézéguet, Francis Sagliocco, Martin Hagedorn, Christophe F. Grosset
2017 OncoTarget  
Glypican-3 (GPC3) is an oncogene, frequently upregulated in liver malignancies such as hepatocellular carcinoma (HCC) and hepatoblastoma and constitutes a potential molecular target for therapy in liver cancer. Using a functional screening system, we identified 10 new microRNAs controlling GPC3 expression in malignant liver cells, five of them e.g. miR-4510, miR-203a-3p, miR-548aa, miR-376b-3p and miR-548v reduce GPC3 expression. These 5 microRNAs were significantly downregulated in tumoral
more » ... ared to non-tumoral liver and inhibited tumor cell proliferation. Interestingly, miR-4510 inversely correlated with GPC3 mRNA and protein in HCC samples. This microRNA also induced apoptosis of hepatoma cells and blocked tumor growth in vivo in the chick chorioallantoic membrane model. We further show that the tumor suppressive effect of miR-4510 is mediated through direct targeting of GPC3 mRNA and inactivation of Wnt/β-catenin transcriptional activity and signaling pathway. Moreover, miR-4510 up-regulated the expression of several tumor suppressor genes while reducing the expression of other pro-oncogenes. In summary, we uncovered several new microRNAs targeting the oncogenic functions of GPC3. We provided strong molecular, cellular and in vivo evidences for the tumor suppressive activities of miR-4510 bringing to the fore the potential value of this microRNA in HCC therapy.
doi:10.18632/oncotarget.17162 pmid:28476031 pmcid:PMC5522324 fatcat:ib7ij6kjunc7ldxxolydyhht7y

The Nuclear Remodeling Induced by Helicobacter Cytolethal Distending Toxin Involves MAFB Oncoprotein

Christelle Péré-Védrenne, Wencan He, Lamia Azzi-Martin, Valérie Prouzet-Mauléon, Alice Buissonnière, Bruno Cardinaud, Philippe Lehours, Francis Mégraud, Christophe F. Grosset, Armelle Ménard
2020 Toxins  
Cells were processed for fluorescent staining with DAPI to detect the nucleus (blue) and fluorescent labelled-phalloidin to detect F-actin (red).  ...  Figure 4 ), Hep3B cells were processed for fluorescent staining with DAPI to detect the nucleus (blue) and fluorescent labelled-phalloidin to detect F-actin (red).  ... 
doi:10.3390/toxins12030174 pmid:32178359 fatcat:223tk72wg5c5teeddfep65tvzu

Tracking cellular and molecular changes in a species-specific manner during experimental tumor progression in vivo

Emilie Indersie, Katarzyna B. Hooks, Caroline Capdevielle, Monique Fabre, Nathalie Dugot-Senant, Angélique Desplat, Sébastien Lepreux, Aksam Merched, Christophe F. Grosset, Martin Hagedorn
2018 OncoTarget  
(F) HBL growth inhibition by cisplatin at T4 and T7 evidenced by tumor weight.  ...  (C-F) Strong immunoreactivity for the proliferation marker Ki-67 and indicated proteins commonly found in hepatoblastoma tissue.  ... 
doi:10.18632/oncotarget.24598 pmid:29662633 pmcid:PMC5882324 fatcat:vdfovibb5nac7lrvqm5jj5k73i

Molecular basis of differential target regulation by miR-96 and miR-182: the Glypican-3 as a model

Sandra Jalvy-Delvaille, Marion Maurel, Vanessa Majo, Nathalie Pierre, Sandrine Chabas, Chantal Combe, Jean Rosenbaum, Francis Sagliocco, Christophe F. Grosset
2011 Nucleic Acids Research  
We therefore pre-depleted Figure S3C-F) . Then depleted cells were transfected with miR-96.  ...  to target GPC3 using Targetscan ( Figure 1B Figure S1E ) (22) , whereas only miR-96 was found amongst the miRNAs predicted using PITA (23) and miRDB (24, 25) (Supplementary Figure S1D and F,  ... 
doi:10.1093/nar/gkr843 pmid:22009679 pmcid:PMC3273822 fatcat:2sndildisjgmzbqu6nnytefoga

MicroRNA therapy inhibits hepatoblastoma growth in vivo by targeting β-catenin and Wnt signaling

Emilie Indersie, Sarah Lesjean, Katarzyna B. Hooks, Francis Sagliocco, Tony Ernault, Stefano Cairo, Maria Merched-Sauvage, Anne Rullier, Brigitte Le Bail, Sophie Taque, Michael Grotzer, Sophie Branchereau (+6 others)
2017 Hepatology Communications  
Hepatoblastoma (HBL) is the most common pediatric liver cancer. In this malignant neoplasm, beta-catenin protein accumulates and increases Wnt signaling due to recurrent activating mutations in the catenin-beta 1 (CTNNB1) gene. Therefore, beta-catenin is a key therapeutic target in HBL. However, controlling beta-catenin production with therapeutic molecules has been challenging. New biological studies could provide alternative therapeutic solutions for the treatment of HBL, especially for
more » ... ed tumors and metastatic disease. In this study, we identified microRNAs (miRNAs) that target beta-catenin and block HBL cell proliferation in vitro and tumor growth in vivo. Using our dual-fluorescence-FunREG system, we screened a library of 1,712 miRNA mimics and selected candidates inhibiting CTNNB1 expression through interaction with its untranslated regions. After validating the regulatory effect of nine miRNAs on beta-catenin in HBL cells, we measured their expression in patient samples. Let-7i-3p, miR-449b-3p, miR-624-5p, and miR-885-5p were decreased in tumors compared to normal livers. Moreover, they inhibited HBL cell growth and Wnt signaling activity in vitro partly through beta-catenin down-regulation. Additionally, miR-624-5p induced cell senescence in vitro, blocked experimental HBL growth in vivo, and directly targeted the beta-catenin 3 0 -untranslated region. Conclusion: Our results shed light on how beta-catenin-regulating miRNAs control HBL progression through Wnt signaling inactivation. In particular, miR-624-5p may constitute a promising candidate for miRNA replacement therapy for HBL patients.
doi:10.1002/hep4.1029 pmid:29404451 pmcid:PMC5721429 fatcat:7h2eyqt4rzhmtj34cpuunpblsa

Cytolethal distending toxin induces the formation of transient messenger-rich ribonucleoprotein nuclear invaginations in surviving cells

Lamia Azzi-Martin, Wencan He, Christelle Péré-Védrenne, Victoria Korolik, Chloé Alix, Martina Prochazkova-Carlotti, Jean-Luc Morel, Emilie Le Roux-Goglin, Philippe Lehours, Mojgan Djavaheri-Mergny, Christophe F. Grosset, Christine Varon (+3 others)
2019 PLoS Pathogens  
(F) Hep3B transgenic cells were cultivated as in Fig 3C.  ...  Cells were stained with fluorescent primary and secondary antibodies targeting UNR (green), DAPI to counterstain the nucleus (blue) and fluorescent-labeled phalloidin to detect F-actin (red, only in D)  ... 
doi:10.1371/journal.ppat.1007921 pmid:31568537 pmcid:PMC6824578 fatcat:kyq4ueybfrae5ar73yp6zig6ci

DUSP9, a Dual-Specificity Phosphatase with a Key Role in Cell Biology and Human Diseases

Fatma Zohra Khoubai, Christophe F Grosset
Mitogen-activated protein kinases (MAPKs) are essential for proper cell functioning as they regulate many molecular effectors. Careful regulation of MAPKs is therefore required to avoid MAPK pathway dysfunctions and pathologies. The mammalian genome encodes about 200 phosphatases, many of which dephosphorylate the MAPKs and bring them back to an inactive state. In this review, we focus on the normal and pathological functions of dual-specificity phosphatase 9 (DUSP9)/MAP kinase phosphatases-4
more » ... KP-4). This cytoplasmic phosphatase, which belongs to the threonine/tyrosine dual-specific phosphatase family and was first described in 1997, is known to dephosphorylate ERK1/2, p38, JNK and ASK1, and thereby to control various MAPK pathway cascades. As a consequence, DUSP9 plays a major role in human pathologies and more specifically in cardiac dysfunction, liver metabolic syndromes, diabetes, obesity and cancer including drug response and cell stemness. Here, we recapitulate the mechanism of action of DUSP9 in the cell, its levels of regulation and its roles in the most frequent human diseases, and discuss its potential as a therapeutic target.
doi:10.3390/ijms222111538 pmid:34768967 pmcid:PMC8583968 fatcat:vmdywgdhxjfndjm3jwiijeo5aq

Some Recent Children's Books in English on Hispanic America

F. Sanchez y Escribano
1941 Hispania  
., 1940 Christopher Columbus Kent, Louise ANDREws, He Went with Christopher Columbus, Boston, Mass., Houghton Mifflin Co., 1940 Spanish Explorers Knoop, FAIrH YINGLING, Quest of the Cavaliers..  ...  Lippincott Co., 1940 Epwarps, FLorENcE Dunn, Menino, New York, Grosset & Dunlop, 1940 Costa Rica Gay, ZHENYA, and CresP1, Pacuita, Manuelito of Costa Rica, New York, Julian Messner, 1940 309  ... 
doi:10.2307/331905 fatcat:tb2hwkvrpbcybmpinssb7rrafe

Page 467 of National Union Catalog Vol. 36, Issue [page]

1963 National Union Catalog  
Mierow, Charles Christopher, 1883- Tr. see Hieronymus, Saint. Letters.  ...  ., Newman Press, 1963- Mierow, Charles Christopher, 1883- ed, and see Otto, Bp. of Freising, d, 1158, The deeds of Frederick Barbarossa, New York, Norton ;1966, Mierow, Charles Christopher, 1883- tr. see  ... 

Page 23 of Library Occurrent Vol. 4, Issue 2 [page]

1915 Library Occurrent  
(F.) Big brother. Page, 50c. Little Colonel series. Page, $1.50 ea. Moores, C. W. Life of Abraham Lincoln for boys and girls. Houghton, 60c. Story of Christopher Columbus for boys and girls.  ...  Grosset, 75c. Hillis, N. D. Quest of John Chapman. Mac- millan, $1.50. Major, Charles. Bears of Blue River. Macmil- lan, 50c. Porter, G (S.) Freckles. Grosset, 50c. Girl of the Limberlost.  ... 

Page 593 of National Union Catalog Vol. 28, Issue [page]

1963 National Union Catalog  
Brit—Examinations, questions, etc. 64-35864 Keenan, Peter B ed, see Shawcross, Christopher Nyholm, 1905- Shawcross and Beaumont on air law. 3rd ed, London, Butterworths, 1966, Keenan, Philip see Morgan  ...  Keenan and John F. McGlynn. New York, Harcourt, Brace & World, Inc. ,:1962) 245 p. 22cm. PPLas NUC63-64473 Keenan, John Richard, Synthetic studies in the pyrrole and indole series.  ... 

Page 329 of National Union Catalog Vol. 24, Issue [page]

1958 National Union Catalog  
Deluxe ed., New York, Grosset & Dunlap ;1961 “ts f is 29 cm. (How and why wonder books, ci?  ...  (Deluxe ed., New York, Grosset & Dunlap ,1962, 48p. fllus. 29cm. (How and why wonder books) 1. Zoology—Juventle Iterature. 1 Title. PZ10.K1282Ht j591 62-9674 f Keen, Maurice.  ... 

Page 175 of JAMA Internal Medicine Vol. 84, Issue 1 [page]

1949 JAMA Internal Medicine  
Morley, Christopher: Modern Essays for Schools, Selected by Christopher Morley.** Moulton, F. R., and Schifferes, J.  ...  Morley, C.: Modern Essays for Schools, Selected by Christopher Morley, New York, Harcourt, Brace & Company, 1921, pp. 129-144. 25. Moulton, F. R., and Schifferes, J.  ... 
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