Assuntos
Neoplasias Hepáticas/genética , Neoplasias Embrionárias de Células Germinativas/genética , Sarcoma/genética , Dineínas do Axonema/genética , Carboxipeptidase B2/genética , Criança , DNA Helicases/genética , Humanos , Masculino , Mutação , Proteínas/genética , Trealase/genética , Sequenciamento do ExomaRESUMO
Necrotizing enterocolitis (NEC) characterized by inflammatory intestinal necrosis is a major cause of mortality and morbidity in newborns. Deep RNA sequencing (RNA-Seq) has recently emerged as a powerful technology enabling better quantification of gene expression than microarrays with a lower background signal. A total of 10 transcriptomes from 5 pairs of NEC lesions and adjacent normal tissues obtained from preterm infants with NEC were analyzed. As a result, a total of 65 genes (57 down-regulated and 8 up-regulated) revealed significantly different expression levels in the NEC lesion compared to the adjacent normal region, based on a significance at fold change ≥ 1.5 and P ≤ 0.05. The most significant gene, DPF3 (P < 0.001), has recently been reported to have differential expressions in colon segments. Our gene ontology analysis between NEC lesion and adjacent normal tissues showed that down-regulated genes were included in nervous system development with the most significance (P = 9.3 × 10â»7; P(corr) = 0.0003). In further pathway analysis using Pathway Express based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, genes involved in thyroid cancer and axon guidance were predicted to be associated with different expression (P(corr) = 0.008 and 0.020, respectively). Although further replications using a larger sample size and functional evaluations are needed, our results suggest that altered gene expression and the genes' involved functional pathways and categories may provide insight into NEC development and aid in future research.
Assuntos
Enterocolite Necrosante/patologia , RNA/metabolismo , Transcriptoma , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Regulação para Baixo , Enterocolite Necrosante/genética , Idade Gestacional , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Projetos Piloto , RNA/química , RNA/isolamento & purificação , Análise de Sequência de RNA , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação para CimaRESUMO
BACKGROUND: Necrotizing enterocolitis (NEC) characterized by intestinal necrosis is one of the most common gastrointestinal emergencies in newborns. The main purpose of this study was to evaluate the whole genome expression levels in a NEC mouse model controlled with breast milk. METHODS: This study induced a NEC model in mice of gestational ages of 18-21 days by intensive hypoxic insult and permitted breast-feeding instead of formula feeding. After evaluating the NEC status in the small intestines of neonatal mice by histological examination, a genome-wide gene expression profile study was completed using microarray analysis. RESULTS: A total of 72 genes (38 down-regulated and 34 up-regulated) were observed to have significantly different expression profiles in the NEC mouse model compared with the normal control animals, based on a significance at fold change ≥ 2 and P < 0.05. In particular, down-regulated Hist1h2aa and up-regulated Ube2i showed the most significant signals (P = 0.0008 for both genes). In an additional gene ontology analysis, the endopeptidase related categories (specifically, serine-type endopeptidase inhibitor activity, P = 8.95 × 10(-5); Pcorr = 0.008) appeared to affect NEC development in the mouse model. CONCLUSION: Although replications and functional evaluations are needed, our results suggest that several genes may have different expression profiles in the NEC mouse model. In particular, endopeptidase related genes (which are also known to be relevant to NEC), as identified through gene ontology analysis, may represent attractive targets for future research.