ABSTRACT
Objective@#To explore potential therapeutic targets for neonatal hypoxic brain injury, we analyzed the effects of hypoxia on the gene expression profiles and signaling pathway in 3D cultured cerebral cortex cells.@*Methods@#R studio software was used to analyze the differentially expressed genes of hypoxia treated cerebral cortex cell data (GSE112137) which was downloaded from GEO database. Gene Oncology and KEGG software were used to enrich the molecular function, biological process and signaling pathways of differentially expressed genes. Then String and Cytoscape software were adapted to analyzed gene interaction network between these genes.@*Results@#There were 395 increasing genes and 185 decreasing genes (Change Fold≥2) were identified in hypoxic cerebral cells compared with the control groups. Most elevated genes were mainly related with molecular function including dioxygenase activity, isomerase activity and misfolded protein binding, while the decreasing genes were enriched in RNA polymerase Ⅱ proximal promoter sequence-specific DNA binding. Biological process enrichment analysis revealed that hypoxia up-regulated genes were associated with endoplasmic reticulum stress, oxidation-reduction process and glycolysis, while down-regulated genes were involved in the progress of neural development and cell differentiation. KEGG pathway enrichment results indicated hypoxia increasing genes were mainly related with endoplasmic reticulum protein processing, glycolysis, amino acid biosynthesis, and decreasing genes were mainly enriched in Parkinson′s disease signaling pathway.@*Conclusions@#Hypoxia in human cerebral cortex cells could cause endoplasmic reticulum stress, protein misfolding and metabolic abnormalities, inhibited the development of neuron cells. Drugs targeting these process may be beneficial to alleviate cerebral hypoxia injury.
ABSTRACT
Objective To explore potential therapeutic targets for neonatal hypoxic brain injury,we analyzed the effects of hypoxia on the gene expression profiles and signaling pathway in 3D cultured cerebral cortex cells.Methods R studio software was used to analyze the differentially expressed genes of hypoxia treated cerebral cortex cell data (GSE112137) which was downloaded from GEO database.Gene Oncology and KEGG software were used to enrich the molecular function,biological process and signaling pathways of differentially expressed genes.Then String and Cytoscape software were adapted to analyzed gene interaction network between these genes.Results There were 395 increasing genes and 185 decreasing genes (Change Fold ≥2) were identified in hypoxic cerebral cells compared with the control groups.Most elevated genes were mainly related with molecular function including dioxygenase activity,isomerase activity and misfolded protein binding,while the decreasing genes were enriched in RNA polymerase Ⅱ proximal promoter sequence-specific DNA binding.Biological process enrichment analysis revealed that hypoxia up-regulated genes were associated with endoplasmic reticulum stress,oxidation-reduction process and glycolysis,while down-regulated genes were involved in the progress of neural development and cell differentiation.KEGG pathway enrichment results indicated hypoxia increasing genes were mainly related with endoplasmic reticulum protein processing,glycolysis,amino acid biosynthesis,and decreasing genes were mainly enriched in Parkinson's disease signaling pathway.Conclusions Hypoxia in human cerebral cortex cells could cause endoplasmic reticulum stress,protein misfolding and metabolic abnormalities,inhibited the development of neuron cells.Drugs targeting these process may be beneficial to alleviate cerebral hypoxia injury.
ABSTRACT
Objective To find potential effective immunotherapy targets for acute myeloid leukemia (AML) by analyzing the expression and clinical significance of different immune checkpoints.Methods Gene expression profiles of AML cell lines (GSE57083) and tissues (GSE37642) were downloaded from GEO database.Then different immune checkpoints expression and clinical significance were analyzed with R studio and GraphPad software.Results In 16 AML cell lines,the expression rank of 11 immune checkpoints genes was LGALS9,PVRL2,PVR,PDCD1,TIM3,CTLA4,PDL1,GITR,LAG3,PDL2,GITRL,and among which LGALS9,PVRL2,GITR had larger variation between different cells.In AML tissues,the expression rank of immune checkpoint was LGALS9,PVRL2,TIM3,PDCD1,CTLA4,LAG3,GITR,PDL1,PVR,GITRL,PDL2.Survival analysis revealed high expression of PVR and LGALS9 was associated with poor prognosis,while the survival time had no significant difference in other genes.Conclusions PVR is highly expressed in AML tumor cells,and LGALS9 is highly expressed in both AML tumor cells and tissues.High expression of PVR and LGALS9 is associated with poor prognosis of AML patients,which may be a potential effective immunotherapy target for AML.