Identification of aberrantly methylated differentially expressed genes targeted by differentially expressed miRNA in osteosarcoma

鉴定骨肉瘤中差异表达 miRNA 靶向的异常甲基化差异表达基因

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作者:Ting-Xuan Wang, Wen-Le Tan, Jin-Cheng Huang, Zhi-Fei Cui, Ri-Dong Liang, Qing-Chu Li, Hai Lu

Background

Osteosarcoma (OS) is the most common primary bone tumors diagnosed in children and adolescents. Recent studies have shown a prognostic role of DNA methylation in various cancers, including OS. The

Conclusions

TSGs including PYCARD, STAT5A, CXCL12 and CXCL14 were aberrantly methylated in OS, and are potential prognostic biomarkers and therapeutic targets. Our findings provide new insights into the role of methylation in OS progression.

Methods

The differentially expressed mRNAs, miRNAs and methylated genes (DEGs, DEMs and DMGs respectively) were screened from various GEO databases, and the potential target genes of the DEMs were predicted by the RNA22 program. The protein-protein interaction (PPI) networks were constructed using the STRING database and visualized by Cytoscape software. The functional enrichment and survival analyses of the screened genes was performed using the R software.

Results

Forty-seven downregulated hypermethylated genes and three upregulated hypomethylated genes were identified that were enriched in cell activation, migration and proliferation functions, and were involved in cancer-related pathways like JAK-STAT and PI3K-AKT. Eight downregulated hypermethylated tumor suppressor genes (TSGs) were identified among the screened genes based on the TSGene database. These hub genes are likely involved in OS genesis, progression and metastasis, and are potential prognostic biomarkers and therapeutic targets. Conclusions: TSGs including PYCARD, STAT5A, CXCL12 and CXCL14 were aberrantly methylated in OS, and are potential prognostic biomarkers and therapeutic targets. Our findings provide new insights into the role of methylation in OS progression.

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