Comprehensive Analysis and Validation Reveal Potential MYCN Regulatory Biomarkers Associated with Prognosis of Neuroblastoma

Background Neuroblastoma (NB) is an embryonic malignant tumor that occurs in the sympathetic nervous system. The treatment effect of patients in the high-risk group is poor, and relapse and treatment failure can occur even with multiple combination treatments. MYCN is an independent prognostic factor for NB, and the proportion of MYCN amplification in tumor tissues of high-risk patients reaches 40-50%. Hence, exploring new MYCN targeting molecules is a meaningful way to treat high-risk NB patients. Methods The microarray datasets were obtained from Gene Expression Omnibus, and differentially expressed genes were identified. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and miRPathDB were used for function and pathway analysis. The STRING and Cytoscape were used to construct a protein-protein interaction network and modular analysis. The miRNet and NetworkAnalyst databases were used to predict and construct target gene-miRNA and target gene-TF networks. The R2 database was used for expression, correlation, and prognosis analysis. The diagnostic effect of the biomarkers was predicted by ROC analysis, and rt-PCR was used to verify the hub genes. Finally, used specific siRNA and plasmid to knockdown and overexpressed MYCN, the mRNA levels were verified. Results We identified 431 DEGs and FBXO9, HECW2, MIB2, RNF19B, RNF213, TRIM36, and ZBTB16 as novel biomarkers that affect the prognosis of the NB patients. In addition, FBXO9, RNF19B, and TRIM36 were preliminarily confirmed to be potential targeting molecules of MYCN. Conclusions Our results are expected to become novel biomarkers for the treatment of high-risk NB patients.

Transcriptome analysis of Valsa mali reveals its response mechanism to the biocontrol actinomycete Saccharothrix yanglingensis Hhs.015

Apple canker is a devastating branch disease caused by Valsa mali (Vm). The endophytic actinomycete Saccharothrix yanglingensis Hhs.015 (Sy Hhs.015) can effectively inhibit the growth of Vm. To reveal the mechanism, by which Vm respond to Sy Hhs.015, the transcriptome of Vm was analyzed using RNA-seq technology. Compared with the control group, 1476 genes were significantly differentially expressed in the treatment group, of which 851 genes were up-regulated and 625 genes were down-regulated. Combined gene function and pathway analysis of differentially expressed genes (DEGs) revealed that Sy Hhs.015 affected the carbohydrate metabolic pathway, which is utilized by Vm for energy production. Approximately 82% of the glycoside hydrolase genes were down-regulated, including three pectinase genes (PGs), which are key pathogenic factors. The cell wall structure of Vm was disrupted by Sy Hhs.015 and cell wall-related genes were found to be down-regulated. Of the peroxisome associated genes, those encoding catalase (CAT) and superoxide dismutase (SOD) which scavenge reactive oxygen species (ROS), as well as those encoding AMACR and ACAA1 which are related to the β-oxidation of fatty acids, were down-regulated. MS and ICL, key genes in glyoxylate cycle, were also down-regulated. In response to the stress of Sy Hhs.015 exposure, Vm increased amino acid metabolism to synthesize the required nitrogenous compounds, while alpha-keto acids, which involved in the TCA cycle, could be used to produce energy by deamination or transamination. Retinol dehydrogenase, associated with cell wall dextran synthesis, and sterol 24-C-methyltransferase, related to cell membrane ergosterol synthesis, were up-regulated. The genes encoding glutathione S-transferase, (GST), which has antioxidant activity and ABC transporters which have an efflux function, were also up-regulated. These results show that the response of Vm to Sy Hhs.015 exposure is a complicated and highly regulated process, and provide a theoretical basis for both clarifying the biocontrol mechanism of Sy Hhs.015 and the response of Vm to stress.

Transcriptome analysis of Valsa mali reveals its response mechanism to the biocontrol actinomycete Saccharothrix yanglingensis Hhs.015

Apple canker is a devastating branch disease caused by Valsa mali (Vm). The endophytic actinomycete Saccharothrix yanglingensis Hhs.015 (Sy Hhs.015) can effectively inhibit the growth of Vm. To reveal the mechanism, by which Vm respond to Sy Hhs.015, the transcriptome of Vm was analyzed using RNA-seq technology. Compared with the control group, 1476 genes were significantly differentially expressed in the treatment group, of which 851 genes were up-regulated and 625 genes were down-regulated. Combined gene function and pathway analysis of differentially expressed genes (DEGs) revealed that Sy Hhs.015 affected the carbohydrate metabolic pathway, which is utilized by Vm for energy production. Approximately 82% of the glycoside hydrolase genes were down-regulated, including three pectinase genes (PGs), which are key pathogenic factors. The cell wall structure of Vm was disrupted by Sy Hhs.015 and cell wall-related genes were found to be down-regulated. Of the peroxisome associated genes, those encoding catalase (CAT) and superoxide dismutase (SOD) which scavenge reactive oxygen species (ROS), as well as those encoding AMACR and ACAA1 which are related to the β-oxidation of fatty acids, were down-regulated. MS and ICL, key genes in glyoxylate cycle, were also down-regulated. In response to the stress of Sy Hhs.015 exposure, Vm increased amino acid metabolism to synthesize the required nitrogenous compounds, while alpha-keto acids, which involved in the TCA cycle, could be used to produce energy by deamination or transamination. Retinol dehydrogenase, associated with cell wall dextran synthesis, and sterol 24-C-methyltransferase, related to cell membrane ergosterol synthesis, were up-regulated. The genes encoding glutathione S-transferase, (GST), which has antioxidant activity and ABC transporters which have an efflux function, were also up-regulated. These results show that the response of Vm to Sy Hhs.015 exposure is a complicated and highly regulated process, and provide a theoretical basis for both clarifying the biocontrol mechanism of Sy Hhs.015 and the response of Vm to stress.