No 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.

O gene c-Src foi o primeiro proto-oncogene descrito, em galinhas, identificado como homólogo celular do gene v-Src, do vírus do sarcoma de Rous, responsável por transformar células normais em cancerosas. c-Src codifica a proteína c-Src, uma tirosina-quinase capaz de fosforilar resíduos de tirosina em diversas proteínas, participando da sinalização celular que ativa processos como a proliferação de células. O artigo apresenta o gene c-SRC que, em humanos, localiza-se no cromossomo 20 e a proteína SRC, o membro protótipo da família SRC de tirosina-quinases não receptoras. Mutações em genes da família SRC têm sido implicadas no desenvolvimento e metástase de tumores humanos e o conhecimento dessas mutações vem possibilitando tratamentos com terapiasalvo utilizando inibidores de tirosina-quinases.