Construction of a circRNA-miRNA-mRNA network based on competitive endogenous RNA reveals the key pathways and central genes of osteosarcoma in vivo

Abstract Circular RNAs (circRNAs) play important roles in a variety of pathological functions. However, the potential functions and detailed mechanisms of circRNAs in osteosarcoma (OS) have not been fully elucidated. In this study, the circRNA, micro RNA (miRNA), and messenger RNA (mRNA) expression profile of human OS was investigated based on the raw microarray data GSE140256, GSE65071 and GSE16088 in Gene Expression Omnibus (GEO) datasets, and seven differentially-expressed circRNAs (DEcircRNAs), 166 differentially-expressed miRNAs (DEmiRNAs), and 175 differentially-expressed mRNAs (DEmRNAs) were identified in total. FunRich was employed to analyze the differentially-expressed transcription factors on the basis of identified DEmiRNAs. In addition, the Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to further study biological functions of the DEmRNAs. Interestingly, post-translational protein modification, collagen-containing extracellular matrix, and single-stranded DNA binding were the most significant pathways enriched for DEmRNAs in GO annotation analysis. Meanwhile, in KEGG pathway enrichment analysis, complement and coagulation cascades, RNA transport and drug metabolism − other enzymes were the most significantly enriched pathways of DEmRNAs in OS. We constructed circRNA-miRNA-mRNA and protein–protein interaction (PPI) networks that may be associated with pathological processes of OS. Finally, we also revealed the pattern of tumor-infiltrating immune cells in OS and further explored the ceRNA networks we constructed in which we found that COL1A1 and RAN were significantly correlated with overall survival in patients with osteosarcoma (p < 0.05). To our knowledge, this study provides the first profile analysis of DEcircRNAs, DEmiRNAs, and DEmRNAs with OS in vivo and reveals a novel idea for understanding the pathogenesis of OS.