Objective Glioblastoma(GBM)is the most common,invasive,and malignant primary brain tumor with a poor prognosis and high recurrence rate.It’s known that some microRNAs(miRNAs)which are associated with tumorigenesis an...Objective Glioblastoma(GBM)is the most common,invasive,and malignant primary brain tumor with a poor prognosis and high recurrence rate.It’s known that some microRNAs(miRNAs)which are associated with tumorigenesis and progression can be considered as prognostic and therapeutic targets in tumors including GBM.This study aims to highlight the potential role of the core miRNAs in GBM and their potential use as a prognostic and therapeutic biomarker.Methods Differentially expressed miRNAs(DEmiRNAs)were identified in GBM by integrating miRNA-sequencing results and a GBM microarray dataset from the Gene Expression Omnibus(GEO)database through bioinformatics tools.The dysregulated miRNAs were identified by survival analysis through Chinese Glioma Genome Atlas(CGGA).Target genes of the dysregulated miRNAs were predicted on MiRWalk and miRTarBase database.TAM2.0 database,Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways analysis were used to analyze the function of the dysregulated miRNAs.Subsequently,protein-protein interaction(PPI)network analysis was used to identify the top 20 hub targets of the up-regulated and down-regulated miRNAs,respectively.Then,core miRNAs in GBM were identified by constructing dysregulated miRNA-differentially expressed hub gene networks.Validation of the core miRNAs expression was detected in 41 GBM tissues compared to 8 normal brain tissues.Furthermore,the potential biomarkers were identified by clinical correlation analysis and survival analysis.Results Totally,68 intersecting DEmiRNAs were identified,40 of which were upregulated and the other 28 miRNAs were downregulated.Two upregulated and 4 downregulated miRNAs showed prognostic significance.Most differentially expressed hub genes were regulated by the miR-28-5p and miR-1224-5p,which were respectively upregulated and downregulated in GBM.The correlation between miR-1224-5p level and recurrence was statistically significant(P=0.011).Survival analysis showed that high miR-28-5p level and high miR-1224-5p level were both associated with better prognosis.Moreover,high miR-1224-5p level was an independent prognosis factor for GBM patients according to the cox regression analysis.Conclusion MiRNA-1224-5p could be a potential target for the prognosis and treatment in GBM.展开更多
基金the National Natural Science Foundation of China(No.81960453 and No.81860445)the Natural Science Foundation of Guangxi Province(No.2018GXNSFAA050151 and No.2018GXNSFAA281251)+2 种基金the Basic Ability Improvement Project for Young and Middle-aged Teachers in Colleges and Universities of Guangxi(No.2020KY03039)the Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University)Ministry of Education(No.GK2018-09,No.GKE 2019-08,and No.GKE-ZZ202006).
文摘Objective Glioblastoma(GBM)is the most common,invasive,and malignant primary brain tumor with a poor prognosis and high recurrence rate.It’s known that some microRNAs(miRNAs)which are associated with tumorigenesis and progression can be considered as prognostic and therapeutic targets in tumors including GBM.This study aims to highlight the potential role of the core miRNAs in GBM and their potential use as a prognostic and therapeutic biomarker.Methods Differentially expressed miRNAs(DEmiRNAs)were identified in GBM by integrating miRNA-sequencing results and a GBM microarray dataset from the Gene Expression Omnibus(GEO)database through bioinformatics tools.The dysregulated miRNAs were identified by survival analysis through Chinese Glioma Genome Atlas(CGGA).Target genes of the dysregulated miRNAs were predicted on MiRWalk and miRTarBase database.TAM2.0 database,Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways analysis were used to analyze the function of the dysregulated miRNAs.Subsequently,protein-protein interaction(PPI)network analysis was used to identify the top 20 hub targets of the up-regulated and down-regulated miRNAs,respectively.Then,core miRNAs in GBM were identified by constructing dysregulated miRNA-differentially expressed hub gene networks.Validation of the core miRNAs expression was detected in 41 GBM tissues compared to 8 normal brain tissues.Furthermore,the potential biomarkers were identified by clinical correlation analysis and survival analysis.Results Totally,68 intersecting DEmiRNAs were identified,40 of which were upregulated and the other 28 miRNAs were downregulated.Two upregulated and 4 downregulated miRNAs showed prognostic significance.Most differentially expressed hub genes were regulated by the miR-28-5p and miR-1224-5p,which were respectively upregulated and downregulated in GBM.The correlation between miR-1224-5p level and recurrence was statistically significant(P=0.011).Survival analysis showed that high miR-28-5p level and high miR-1224-5p level were both associated with better prognosis.Moreover,high miR-1224-5p level was an independent prognosis factor for GBM patients according to the cox regression analysis.Conclusion MiRNA-1224-5p could be a potential target for the prognosis and treatment in GBM.
