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.

[Retracted] DNMT3A Regulates miR‐149 DNA Methylation to Activate NOTCH1/Hedgehog Pathway to Promote the Development of Junctional Osteosarcoma

“…OS is the most prevalent malignant bone tumor, and it has a significant impact on patients' quality of life and life expectancy. Early detection and treatment of osteosarcoma patients cannot be overstated [ 16 ]. It has an early onset age, a high malignancy, a high rate of metastasis, and a bad prognosis [ 17 ].…”

Epidemiological Evidence for Associations Between Genetic Variants and Osteosarcoma Susceptibility: A Meta-Analysis

“…The excision repair cross-complementation 3 ( ERCC3 ) gene encodes a DNA helicase that plays an important role in nucleotide excision repair. The polymorphisms of ERCC3 have been reported to be associated with several cancers, such as colorectal cancer, pancreatic cancer, breast cancer, and OS ( 5 , 31 , 32 ). The potential mechanism of OS susceptibility was deemed to be its functions as rate-limiting enzymes in the NER pathway ( 33 ).…”

“…Although current treatment strategy, including neoadjuvant therapy prior to wide margin surgical resection and followed by postoperative chemotherapy, greatly improves long-term survival rate to about 70%, its outcome is not satisfactory (3). The pathogenesis of OS is a complex, multistep and multifactorial process in which interactions between genetic and environment factors are proposed to be related to the progression of OS (4,5). Single nucleotide polymorphisms (SNPs) have been reported to be involved in DNA repair, growth regulation, antigen processing and presentation, which may be implicated in the pathogenesis of OS (6)(7)(8).…”

Clinical significance and effect of PRR 11 up-regulation on the malignancy of osteosarcoma

“…Oncology research has thus been ushered into the era of "data explosion". Bioinformatic methods have been used to screen tumor mRNA [4], circRNAs [5], lncRNA [6], the circRNA-miRNA-mRNA network [7], tumor microenvironment genes [8], and N6-methyladenosine [9]. Although there have been several studies, the clinical outcomes of patients with osteosarcoma have not significantly improved; there-fore, the identification of new effective treatments is critical.…”