No abstract

Several studies have already identified the prognostic markers in colorectal cancer (CRC) based on somatic copy number alteration (SCNA). However, very little information is available regarding their value as a prognostic marker. Gene dosage effect is one important mechanism of copy number and dosage-sensitive genes are more likely to behave like driver genes. In this work, we propose a new pipeline to identify the dosagesensitive prognostic genes in CRC. The RNAseq data, the somatic copy number of CRC from TCGA were assayed to screen out the SCNAs. Wilcoxon rank-sum test was used to identify the differentially expressed genes in alteration samples with |SCNA| > 0.3. Coxregression was used to find the candidate prognostic genes. An iterative algorithm was built to identify the stable prognostic genes. Finally, the Pearson correlation coefficient was calculated between gene expression and SCNA as the dosage effect score. The cell line data from CCLE was used to test the consistency of the dosage effect. The differential coexpression network was built to discover their function in CRC. A total of six amplified genes (NDUFB4, WDR5B, IQCB1, KPNA1, GTF2E1, and SEC22A) were found to be associated with poor prognosis. They demonstrate a stable prognostic classification in more than 50% threshold of SCNA. The average dosage effect score was 0.5918 ± 0.066, 0.5978 ± 0.082 in TCGA and CCLE, respectively. They also show great stability in different data sets. In the differential co-expression network, these six genes have the top degree and are connected to the driver and tumor suppressor genes. Function enrichment analysis revealed that gene NDUFB4 and GTF2E1 affect cancer-related functions such as transmembrane transport and transformation factors. In conclusion, the pipeline for identifying the prognostic dosagesensitive genes in CRC was proved to be stable and reliable.

Background Salmonella enterica serovar Enteritidis (SE) is one of the food-borne pathogenic bacteria, which affects poultry production and poses severe threat to human health. The correlation of immune system and metabolism in chicken after SE inoculation is important but not clear. In the current study, we identified the expression of immune and energy metabolism related genes using quantitative PCR to evaluate the correlation between immune system and energy metabolism against SE inoculation in Jining Bairi chicken. Results ATP5G1, ATP5G3 and ND2 were significantly up-regulated at 1 dpi (day post inoculation), and ATP5E, ATP5G1, ATP5G3 were significantly down-regulated at 7 dpi ( P < 0.05). IL-8 and IL-1 β were significantly down-regulated at 1 dpi, IL-8 and IL-18 were significantly down-regulated at 3 dpi, IL-8 and BCL10 were significantly up-regulated at 7 dpi ( P < 0.05). Conclusions These findings indicate that the correlation between immune and energy metabolism related genes gradually change with time points post SE inoculation, from one homeostasis to an opposite homeostasis with 3 dpi as a turning point. These results will pave the foundation for the relationship between immune system and energy metabolism in the response to SE inoculation in chicken.

By combining the experiments of reciprocal crosses of chicken infected with Salmonella enterica serovar Enteritidis (S. Enteritidis), we focused on the common response of cecal microbiota to an inflammatory state in respect of transcriptome and microbiome. The inoculation of S. Enteritidis improved the microbial diversity and promoted the microbiota evolution in our infection model. Correlation analysis between bacteria and inflammation-related genes showed that some intestinal microorganisms were “inflammophile” and thrived in an inflamed environment. The global function of cecal microbiome was to maintain the homeostasis likely by the up-regulation of microbial metabolism pathway in bacitracin, putrescine, and flavonoids production, although the bacitracin may affect the symbiotic bacteria Enterococcus. The action of S. Enteritidis had close relationships with multiple inflammation-related genes, including the genes PTAFR, LY96, and ACOD1 which proteins are related to the binding and tolerance of LPS, and the genes IL-18, IL-18R1 and IL-18RAP which products can form a functional complex and transmit IL-18 pro-inflammatory signal. Additionally, the infection of S. Enteritidis aroused the transcription of EXFABP, which protein has a potential to sequestrate the siderophore and might cause the decline of Escherichia-Shigella and Enterococcus. S. Enteritidis can escape from the sequestrating through the salmochelin, another kind of siderophore which cannot be recognized by EXFABP. Probably by this way, S. Enteritidis competed with the symbiotic bacteria and edged out the niches. Our research can help to understand the interplay between host, pathogen, and symbiotic bacteria.

Background Salmonella enterica, serovar Enteritidis (SE) is a food-borne pathogen, which can cause great threat to human health through consumption of the contaminated poultry products. Chicken is the main host of SE. The mRNA and microRNA (miRNA) expression profiles were analyzed on cecum of Shouguang chicken via next-generation sequencing and bioinformatics approaches. The treated group was inoculated SE, and the control group was inoculated with phosphate buffer saline (PBS). Results There were 1760 differentially expressed mRNAs in the SE-infected group, of which 1046 were up-regulated mRNA, and 714 were down-regulated mRNA. In addition, a total of 821 miRNAs were identified, and 174 miRNAs were differentially expressed, of which 100 were up-regulated and 74 were down-regulated. Functional enrichment of differentially expressed mRNAs was similar to miRNA target genes. The functional analysis results of differentially expressed mRNAs and miRNAs were performed. Immune-related processes and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways were enriched by up-regulated mRNA. The down-regulated mRNAs were enriched in tissue development and metabolic-related KEGG pathways. The functional analysis of up-regulated miRNA target genes was similar to the down-regulated mRNAs. The down-regulated miRNA target genes were enriched in metabolic-related GO (Gene Ontology) -BP (Biological process) terms and KEGG pathways. The overlap of the up-regulated mRNA and the up-regulated miRNA target genes (class I) was 325, and the overlap of the down-regulated miRNA target genes (class II) was 169. The class I enriched in the immune-related GO-BP terms and KEGG pathways. The class II mainly enriched in metabolic-related GO-BP terms and KEGG pathways. Then we detected the expression of mRNA and miRNA through qRT-PCR. The results shown that the expression of HHIP, PGM1, HTR2B, ITGB5, RELN, SFRP1, TCF7L2, SCNN1A, NEK7, miR-20b-5p, miR-1662, miR-15a, miR-16-1-3p was significantly different between two groups. Dual-luciferase reporter assay was used to detect the relationship between miR-20b-5p and SCNN1A. The result indicated that miR-20b-5p regulate immune or metabolic responses after SE infection in Shouguang chickens by directly targeting SCNN1A. Conclusions The findings here contribute to the further analysis of the mechanism of mRNA and miRNA defense against SE infection, and provide a theoretical foundation for the molecular disease-resistant breeding of chickens.