Expressão diferencial de genes regulados pelo MYC em linhagens de câncer gástrico

Abstract

MYC is an oncogene responsible for excessive cell growth in cancer, allowing the transcriptional activation of genes involved in cell cycle regulation, metabolism and apoptosis, and is generally overexpressed in Gastric Cancer (GC). Using siRNA and Next Generation Sequencing (NGS), we identified the Genes Differential Expression (DEGs) regulated by MYC in three Brazilian cell lines of GC represented by the diffuse, intestinal and metastatic histological subtypes, and later integrated these data with a computational gene enrichment with the GSEA (Gene Set Enrichment Analysis) tool. We identified a total of 5,471 DEGs with a high correlation (80%). The silencing of MYC by siRNA in diffuse and metastatic CG cell lines resulted in an increase in the number of DEGs with decreased expression, while in intestinal-type lineage they exhibited a greater amount of DEGs with an increased expression profile. From gene enrichment, using our sequenced samples compared to the hallmark gene sets, we found 11 significant sets of genes enriched mainly in the following categories of processes: proliferation, pathway, metabolic signaling and DNA damage. Subsequently, DEGs were enriched in the metabolic pathways of the KEGG (Kyoto Encyclopedia of Genes and Genomes) database, and 12 enriched pathways were found that added a variety of biological functions, and three of them were common to all three cell lines of GC: ubiquitin-mediated proteolysis, ribosomes, system and epithelial cell signaling in Helicobacter pylori infection. In this study, GC cell lines shared 14 genes regulated by MYC, but their gene expression profile was different for each histological subtype. Therefore, the results of the in silico analysis of this study revealed expression signatures related to MYC in GC. Thus, we present evidence that these CG cell lines, represented by distinct histological subtypes, have different expression profiles regulated by MYC, but share a common nucleus of genes with altered profiles. This is an important step towards understanding the role of MYC in gastric carcinogenesis, as well as an indication of probable new drug targets in stomach cancer.