The role of significantly deregulated MicroRNAs in osteosarcoma based on bioinformatic analysis

Abstract

OBJECTIVE: This study aimed to identify potential key microRNAs (miRNAs) in osteosarcoma and construct miRNA-mRNA negative regulatory networks through analysis of the Gene Expression Omnibus (GEO) database. METHODS: The differentially expressed miRNAs (DE-miRNAs) in GSE28423 were screened, and their prognostic value was assessed with the prognostic data of GSE39058. The target genes of prognostic DE-miRNAs were predicted and underwent Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. In addition, the expression of all predicted target genes were assessed using the mRNA array data of GSE28424. Finally, the gene-drug interaction network was constructed. RESULTS: We identified 205 DE-miRNAs between osteosarcoma cells and normal bone. Among them, high expression of miR-411-3p and miR-487b-5p were correlated with prolonged survival. Furthermore, 2659 genes predicted as targets of miR-411-3p or miR-487b-5p were clustered in 42 significant GO categories, including “regulation of neurotransmitter secretion” and “phosphoprotein binding”, as well as 23 significant KEGG pathways, such as “MAPK signaling pathway” and “Ras signaling pathway”. Five of the 75 overlapping target genes of miR-411-3p and miR-487b-5p were downregulated in osteosarcoma, including ZBTB20, ADAMTS4, GLIPR2, CLIC5 and CBX7. CONCLUSIONS: Our findings might help clarify molecular mechanisms underlying the oncogenesis and development, and offer potential targets for osteosarcoma.