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Introduction Issn: 2230-9926 Available online at http://www.journalijdr.com ISSN: 2230-9926 International Journal of Development Research Vol. 09, Issue, 11, pp. 31893-31899, November, 2019 RESEARCH ARTICLE OPEN ACCESS TUMOR DORMANCY IN POPULATION OF CANCER STEM CELLS: GENE INTERACTIONS BY BIOINFORMATICS 1,2João Vitor da Silva Rodrigues, 1Franciele Ornelas Cunha, 1,3Daniela Oliveira Lima Magalhães, 1,4Guilherme Araújo Lacerda, 1,2Jéssica Nayara Basílio Silva, 1Amanda Rodrigues Santos, 1Valéria Couto Quintão Eleoterio, 1,5André Luiz Senna Guimarães, 1,5Alfredo Maurício 1,3 Batista De-Paula and * Ludmilla Regina de Souza David 1Universidade Estadual de Montes Claros, 39401-001, Montes Claros, MG, Brazil; 2Universidade Federal de Viçosa, 36570- 900, Viçosa, MG, Brazil; 3Faculdades Promove, Belo Horizonte-MG; 4Department of Biology. Universidade Estadual de Montes Claros, 39401-001, Montes Claros, MG, Brazil; 5Department of Dentistry. Universidade Estadual de Montes Claros, 39401-001, Montes Claros, MG, Brazil . ARTICLE INFO ABSTRACT Article History: Introduction: Cancer stem cells (CSC) correspond to a small population of cells tumor with the Article History: ReceivedReceived 27xxxxxx,th August 2019, 2019 ability to remain hidden. This contributes strongly to the resistance to antitumor therapies, the ReceivedReceived inin revisedrevised formform occurrence of relapse and metastasis. Objective: Inter relate the gene interactions 03xxxxxxxx,rd September 201,9 2019 networks of tumor dormancy (TD) and CSC. Methods: Genetic interaction networks of CSC and AcceptedAccepted 03xxxxxxxxxrd October, ,20 201919 DT were identified in the Gene Cards® database. The maps of genomic interactions were PublishedPublished onlineonline 30xxxxxth November, 2019 , 2019 performed using the software STRING 10.0. The cluster analysis of the genes was performed in the SPSS® Statistic 18.0.DT network genes present in the CSC were identified. Dormancy Key Words: markers were analyzed for the interactions performed in both networks. Results: 386 and42genes Tumor stem cells; Quiescence, belonging to the CSC and TD networks, respectively, were identified. TP53, MYC, AKT1, Biomarkers, gene interaction network, CTNNB1, JUN andSTAT3 genes were considered the leading of the CSC. The leading genes of Genomic map. TD were AKT1,CDK2, MAP2K4, PCNA, VEGFA and MCM2. The dormancy presented 12 genes common to CSC, with prominence for AKT1, considered leader in both conditions. All of *Corresponding author: the dormancy markers were identified in the CSC network, with between 8and 13 interactions Ludmila Regina de Souza David performed per gene. Conclusion: Twelve genes common to the TD and CSC networksratify the interrelation between them. Copyright © 2019, João Vitor da Silva Rodrigues 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. Citation: João Vitor da Silva Rodrigues, Franciele Ornelas Cunha, Daniela Oliveira Lima Magalhães et al. 2019. “Tumor dormancy in population of cancer stem cells: gene interactions by bioinformatics”, International Journal of Development Research, 09, (11), 31893-31899. INTRODUCTION prostate, colon, stomach, ovary, head and neck cancer, among others (Singh, 2013). The plasticity of CSCs gives them the Cancerous Stem Cells (CSC) correspond to a small population potential for survival in an unknown environment, which is of tumor cells capable of self-renewal and differentiate into all largely due to the increase in their genetic instabilities. When tumor cell types. These cells do not actively proliferate and are the epithelial tumor cell spreads towards the mesenchyme, in demonstrably resistant to various cytotoxic treatments the epithelial-mesenchymal transition phenomenon, the targeting cells in mitotic activity. In the treatment of epithelial cell undergoes biochemical, molecular and patientswith cancer, the presence of tumor cells in the state of morphological changes that confers to it a mesenchymal cell dormancy diminishes the effectiveness of the therapeutic phenotype. This process is facilitated by the tumor response and allows them to remain undetectable for long microenvironment, but is a behavior strongly present in the periods, favoring the occurrence of recurrences and metastases CSC phenotype (Pascussiet al., 2016; Konrad et al., 2017). It (Dean, 2005; Yang et al., 2016). CSC were first identified in is also proposed that a population known as Metastatic Cancer human acute myeloid leukemia and later in several solid Stem Cells (mCSC) and its progenies manipulate the tumor tumors, such as breast, brain, lung, liver, pancreas, melanoma, microenvironment and influence the biology of the metastatic niches. 31894 João Vitor da Silva Rodrigues et al., Tumor dormancy in population of cancer stem cells: gene interactions by bioinformatics Table 1. Genes common to the networks of gene interaction of tumoral dormancy and cancer stem cells Genes Descriptions * AKT1 AKT Serine / Threonine Kinase 1, also referred to as kinase B, is known as an oncogene. It participates in the regulation of several cellular processes, including metabolism, proliferation, cell survival, growth and angiogenesis. CD82 ThemoleculeCD82 is a membrane glycoprotein related to the reduction of the tumor progression of human cancers. CXCR4 C-X-C MotifChemokine Receptor 4 acts as a receptor for extracellular ubiquitin; participates in the events of hematopoiesis. DLL4 Delta Like Canonical NotchLigand 4 is involved in the Notch signaling pathway, which includes events related to cell proliferation, death and differentiation, and angiogenesis. MAPK14 Mitogen-ActivatedProteinKinase14 is a kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 plays an important role in the cascades of cellular responses leading to the direct activation of transcription factors. MTOR Mechanistic Target ofRapamycinKinase is a serine / threonine p rotein kinase that is a central regulator of cell metabolism, growth, and survival. NOTCH3 NeurogenicLocusNotchHomologProtein 3 is a receptor for membrane bound ligands Jagged1, Jagged2 and Delta1 to regulate the determination of cell fate and is involved in the implementation of differentiation, proliferation and apoptosis programs. NOTCH4 NeurogenicLocusNotchHomologProtein 4 is a receptor for membrane bound ligands Jagged1, Jagged2 and Delta1 to regulate the determination of cell fate and is involved in the implementation of differentiation, proliferation and apoptosis programs. PTK2 Protein TyrosineKinase 2 is a protein kinase that plays a key role in regulating cell migration, adhesion, scattering, cytoskeletal reorganization, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, and apoptosis. SOX2 Sex DeterminingRegion Y-Box 2 is a transcription factor that forms a trimeric complex with OCT4 in DNA and controls the expression of several genes involved in embryonic development, such as YES1, FGF4, UTF1 and ZFP206. SPP1 SecretedPhosphoprotein 1 acts as a cytokine involved in increased production of interferon-gamma and interleukin-12, and reduced production of interleukin-10, being essential in type I immunity. VEGFA Vascular Endothelial Growth Factor A is an active growth factor in angiogenesis, vasculogenesis and endothelial cell growth. It promotes cell migration, inhibits apoptosis, and induces permeabilization of blood vessels. * Genesinformation were obtained from the Genecards database. In the new site, mCSCs may actively proliferate or become Construction and analysis of maps of genomic interaction dormant, and niche stimulating factors may lead to CSC reactivation and metastatic lesion formation (Li et al., 2007). After selecting all the genes belonging to each biological Many of the factors that maintain dormant cells also influence condition, a genomic map of each situation was constructed CSC behavior. It is believed that three mechanisms are using the software STRING (Szklarczyk et al., 2015), using all involved in the dormancy of cancer cells, such astumor sources of active interactions in the species Homo sapiens (text microenvironment factors that maintain the cells in the G0 mining, experiments, database, co-expression, neighborhood, phase of the cell cycle, the low vascularization around the fusion of genes and co-occurrence) that had a confidence level tumor and the marked immune response against tumor cells above 0.9. Gene network mapping analysis in the STRING (Evans and Lin, 2015). Immune quiescence and escape are database resulted in afile Text Output containing the scores for hallmarks of some CSCs (Kleffels and Schattont, 2013). From all associations made by each gene in the study network. Thus, these evidences, it is understood that new methodologies that such scores were tabulated in Excel 2013 program, together contribute to the understanding of the biology of the tumor, with the associations of each gene in the network under and especially the CSC, need to be explored. Biomarkers are consideration and multiplied by 1000, in order to meet a single fundamental in this process, and are commonly used in many score, the weighted number of connections(Weighted Number applications (Califf, 2018). In this scenario, bioinformatics of Links (WNL)) (Poswaret al., 2015). In this study, we also tools have received considerable attention in the interpretation calculated the overall score of genes called
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