Gastric Cancer Cell Lines Have Different MYC-Regulated Expression Patterns but Share a Common Core of Altered Genes
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-r...
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Series: | Canadian Journal of Gastroenterology and Hepatology |
Online Access: | http://dx.doi.org/10.1155/2018/5804376 |
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doaj-492f767527f245cd896b1160a4f5d4982020-11-25T00:47:13ZengHindawi LimitedCanadian Journal of Gastroenterology and Hepatology2291-27892291-27972018-01-01201810.1155/2018/58043765804376Gastric Cancer Cell Lines Have Different MYC-Regulated Expression Patterns but Share a Common Core of Altered GenesJersey Heitor da S. Maués0Helem Ferreira Ribeiro1Giovanny R. Pinto2Luana de Oliveira Lopes3Letícia M. Lamarão4Carla Mariana F. Pessoa5Caroline de Fátima Aquino Moreira-Nunes6Raimundo Miranda de Carvalho7Paulo P. Assumpção8Juan A. Rey9Rommel M. Rodríguez Burbano10Human Cytogenetics Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém, BrazilHuman Cytogenetics Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém, BrazilDepartment of Biomedicine, Federal University of Piauí, Parnaíba, BrazilDepartment of Biomedicine, Federal University of Piauí, Parnaíba, BrazilLaboratory of Nucleic Acids, State Center of Hematology and Hemotherapy, Belém, BrazilOncology Research Nucleus, University Hospital João de Barros Barreto, Federal University of Pará, Belém, BrazilLaboratory of Pharmacogenetics, Drug Research and Development Center, Federal University of Ceará, Fortaleza, BrazilLaboratory of Molecular Biology, Ophir Loyola Hospital, Belém, BrazilOncology Research Nucleus, University Hospital João de Barros Barreto, Federal University of Pará, Belém, BrazilMolecular Oncogenetics Laboratory, Research Unit, Hospital Universitario La Paz, Madrid, SpainLaboratory of Molecular Biology, Ophir Loyola Hospital, Belém, BrazilMYC 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.http://dx.doi.org/10.1155/2018/5804376 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jersey Heitor da S. Maués Helem Ferreira Ribeiro Giovanny R. Pinto Luana de Oliveira Lopes Letícia M. Lamarão Carla Mariana F. Pessoa Caroline de Fátima Aquino Moreira-Nunes Raimundo Miranda de Carvalho Paulo P. Assumpção Juan A. Rey Rommel M. Rodríguez Burbano |
spellingShingle |
Jersey Heitor da S. Maués Helem Ferreira Ribeiro Giovanny R. Pinto Luana de Oliveira Lopes Letícia M. Lamarão Carla Mariana F. Pessoa Caroline de Fátima Aquino Moreira-Nunes Raimundo Miranda de Carvalho Paulo P. Assumpção Juan A. Rey Rommel M. Rodríguez Burbano Gastric Cancer Cell Lines Have Different MYC-Regulated Expression Patterns but Share a Common Core of Altered Genes Canadian Journal of Gastroenterology and Hepatology |
author_facet |
Jersey Heitor da S. Maués Helem Ferreira Ribeiro Giovanny R. Pinto Luana de Oliveira Lopes Letícia M. Lamarão Carla Mariana F. Pessoa Caroline de Fátima Aquino Moreira-Nunes Raimundo Miranda de Carvalho Paulo P. Assumpção Juan A. Rey Rommel M. Rodríguez Burbano |
author_sort |
Jersey Heitor da S. Maués |
title |
Gastric Cancer Cell Lines Have Different MYC-Regulated Expression Patterns but Share a Common Core of Altered Genes |
title_short |
Gastric Cancer Cell Lines Have Different MYC-Regulated Expression Patterns but Share a Common Core of Altered Genes |
title_full |
Gastric Cancer Cell Lines Have Different MYC-Regulated Expression Patterns but Share a Common Core of Altered Genes |
title_fullStr |
Gastric Cancer Cell Lines Have Different MYC-Regulated Expression Patterns but Share a Common Core of Altered Genes |
title_full_unstemmed |
Gastric Cancer Cell Lines Have Different MYC-Regulated Expression Patterns but Share a Common Core of Altered Genes |
title_sort |
gastric cancer cell lines have different myc-regulated expression patterns but share a common core of altered genes |
publisher |
Hindawi Limited |
series |
Canadian Journal of Gastroenterology and Hepatology |
issn |
2291-2789 2291-2797 |
publishDate |
2018-01-01 |
description |
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. |
url |
http://dx.doi.org/10.1155/2018/5804376 |
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