Integral Analyses of Competing Endogenous RNA Mechanisms and DNA Methylation Reveal Regulatory Mechanisms in Osteosarcoma

Abstract

Background: Osteosarcoma (OS) is the most common primary malignant bone tumour in children and adolescents, with rapid growth, frequent metastasis, and a poor prognosis, but its pathogenesis has not been fully elucidated. Exploring the pathogenesis of OS is of great significance for improving diagnoses and finding new therapeutic targets.Methods: Differentially expressed circRNAs (DECs), miRNAs (DEMs), methylated DNA sites (DMSs), and mRNAs (DEGs) were identified between OS and control cell lines. GSEA of DEGs and functional enrichment analysis of methylated DEGs were carried out to further identify potential biological processes. Online tools were used to predict the miRNA binding sites of DECs and the mRNA binding sites of DEMs, and then construct a circRNA-miRNA-mRNA network. Next, an analysis of the interaction between methylated DEGs was performed with a protein-protein interaction (PPI) network, and hub gene identification and survival analysis were carried out. The expression pattern of circRNA-miRNA-mRNA was validated by real-time PCR.Results: GSEA and functional enrichment analysis indicated that DEGs and methylated DEGs are involved in important biological processes in cancer. Hsa_circ_0001753/has_miR_760/CD74 network was constructed and validated in cell lines. Low expression levels of CD74 are associated with poor overall survival times and show good diagnostic ability.Conclusion: Methylated DEGs may be involved in the development of OS, and the hsa_circ_0001753/has_miR_760/CD74 network may serve as a target for the early diagnosis of and targeted therapy for OS.