CpG methylation patterns are associated with gene expression variation in osteosarcoma

  • Authors:
    • Qiang Wang
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  • Published online on: May 26, 2017     https://doi.org/10.3892/mmr.2017.6635
  • Pages: 901-907
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Abstract

Osteosarcoma is a common malignant tumor in childhood and adolescence (nearly 5% of all cases of cancer in children), as well as a type of tumor with poor prognosis. However, the pathogenesis and molecular mechanisms of osteosarcoma remains to be elucidated. The aim of the current study was to determine the association between methylation and gene expression changes in osteosarcoma cell line. Microarray data were obtained from the Gene Expression Omnibus database (GSE36004). Genome‑wide methylation status was determined in 19 different osteosarcoma cell lines and 6 normal controls. Differentially expressed genes (DEGs) were identified from cancer cells with genefilter package in R and differentially methylated sites were screened with CpGassoc package in R. Integrated gene expression with methylation profiles, genes differentially expressed and methylated, were obtained, and transcriptional regulatory network construction was performed. Functional annotation was performed for genes in the network using the DAVID online tool. Following integrated analysis, a total of 75 methylated sites were demonstrated to be localized at a transcription factor binding region. These sites may be bound by 83 transcription factors which will then alter the expression of 75 downstream DEGs. In the regulatory network, seizure related 6 homolog like 2 (SEZ6L2) had the highest degree of upregulation and was demonstrated to be regulated by 12 transcription factors. Furthermore, kin of IRRE like (KIRREL), centrosomal protein 72 (CEP72) and cyclin‑dependent kinase 4 (CDK4) were also regulated by more than three transcription factors. Functional annotation revealed that the upregulated genes were primarily involved in the cell cycle pathway. Several differentially methylated sites were associated with upregulation of SEZ6L2, KIRREL, CEP72 and CDK4 and may have an important role in the pathogenesis of osteosarcomas through promotion of cell proliferation and metastasis.
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July-2017
Volume 16 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Wang Q: CpG methylation patterns are associated with gene expression variation in osteosarcoma. Mol Med Rep 16: 901-907, 2017
APA
Wang, Q. (2017). CpG methylation patterns are associated with gene expression variation in osteosarcoma. Molecular Medicine Reports, 16, 901-907. https://doi.org/10.3892/mmr.2017.6635
MLA
Wang, Q."CpG methylation patterns are associated with gene expression variation in osteosarcoma". Molecular Medicine Reports 16.1 (2017): 901-907.
Chicago
Wang, Q."CpG methylation patterns are associated with gene expression variation in osteosarcoma". Molecular Medicine Reports 16, no. 1 (2017): 901-907. https://doi.org/10.3892/mmr.2017.6635