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      Gastric Cancer Cell Lines Have Different MYC-Regulated Expression Patterns but Share a Common Core of Altered Genes

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          Abstract

          MYC is an oncogene responsible for excessive cell growth in cancer, enabling transcriptional activation of genes involved in cell cycle regulation, metabolism, and apoptosis, and is usually overexpressed in gastric cancer (GC). By using siRNA and Next-Generation Sequencing (NGS), we identified MYC-regulated differentially expressed Genes (DEGs) in three Brazilian gastric cancer cell lines representing the histological subtypes of GC (diffuse, intestinal, and metastasis). The DEGs were picked using Sailfish software, followed by Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis using KEGG. We found 11 significantly enriched gene sets by using enrichment score (ES), False Discovery Rate (FDR), and nominal P-values. We identified a total of 5.471 DEGs with correlation over (80%). In diffuse-type and in metastatic GC cell lines, MYC-silencing caused DEGs downregulation, while the intestinal-type GC cells presented overall DEGs upregulation after MYC siRNA depletion. We were able to detect 11 significant gene sets when comparing our samples to the hallmark collection of gene expression, enriched mostly for the following hallmarks: proliferation, pathway, signaling, metabolic, and DNA damage response. When we analyzed our DEGs considering KEGG metabolic pathways, we found 12 common branches covering a wide range of biological functions, and three of them were common to all three cell lines: ubiquitin-mediated proteolysis, ribosomes, and system and epithelial cell signaling in Helicobacter pylori infection. The GC cell lines used in this study share 14 MYC-regulated genes, but their gene expression profile is different for each histological subtype of GC. Our results present a computational analysis of MYC-related signatures in GC, and we present evidence that GC cell lines representing distinct histological subtypes of this disease have different MYC-regulated expression profiles but share a common core of altered genes. This is an important step towards the understanding of MYC's role in gastric carcinogenesis and an indication of probable new drug targets in stomach cancer.

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          Most cited references42

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          The control of the false discovery rate in multiple testing under dependency

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            Computational methods for transcriptome annotation and quantification using RNA-seq.

            High-throughput RNA sequencing (RNA-seq) promises a comprehensive picture of the transcriptome, allowing for the complete annotation and quantification of all genes and their isoforms across samples. Realizing this promise requires increasingly complex computational methods. These computational challenges fall into three main categories: (i) read mapping, (ii) transcriptome reconstruction and (iii) expression quantification. Here we explain the major conceptual and practical challenges, and the general classes of solutions for each category. Finally, we highlight the interdependence between these categories and discuss the benefits for different biological applications.
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              Sailfish enables alignment-free isoform quantification from RNA-seq reads using lightweight algorithms

              We introduce Sailfish, a computational method for quantifying the abundance of previously annotated RNA isoforms from RNA-seq data. Because Sailfish entirely avoids mapping reads, a time-consuming step in all current methods, it provides quantification estimates much faster than do existing approaches (typically 20 times faster) without loss of accuracy. By facilitating frequent reanalysis of data and reducing the need to optimize parameters, Sailfish exemplifies the potential of lightweight algorithms for efficiently processing sequencing reads.
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                Author and article information

                Contributors
                Journal
                Can J Gastroenterol Hepatol
                Can J Gastroenterol Hepatol
                CJGH
                Canadian Journal of Gastroenterology & Hepatology
                Hindawi
                2291-2789
                2291-2797
                2018
                16 October 2018
                : 2018
                : 5804376
                Affiliations
                1Human Cytogenetics Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
                2Center of Biological and Health Sciences, Department of Biomedicine, University of Amazon, Belém, Brazil
                3Department of Biomedicine, Federal University of Piauí, Parnaíba, Brazil
                4Laboratory of Nucleic Acids, State Center of Hematology and Hemotherapy, Belém, Brazil
                5Oncology Research Nucleus, University Hospital João de Barros Barreto, Federal University of Pará, Belém, Brazil
                6Laboratory of Pharmacogenetics, Drug Research and Development Center, Federal University of Ceará, Fortaleza, Brazil
                7Laboratory of Molecular Biology, Ophir Loyola Hospital, Belém, Brazil
                8Molecular Oncogenetics Laboratory, Research Unit, Hospital Universitario La Paz, Madrid, Spain
                Author notes

                Guest Editor: Kiran L. Sharma

                Author information
                http://orcid.org/0000-0001-5570-3158
                http://orcid.org/0000-0002-4798-6183
                Article
                10.1155/2018/5804376
                6206580
                30410872
                d94538c0-a4e9-4025-ab52-9288b453b9c0
                Copyright © 2018 Jersey Heitor da S. Maués et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 April 2018
                : 12 September 2018
                : 23 September 2018
                Funding
                Funded by: Conselho Nacional de Desenvolvimento Científico e Tecnológico
                Award ID: 402283/2013
                Award ID: 471072/2012-5
                Funded by: FAPESPA
                Award ID: 123/2014
                Funded by: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
                Award ID: 17704/12-0
                Categories
                Research Article

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