Prediction of circRNAs Based on the DNA Methylation-Mediated Feature Sponge Function in Breast Cancer

Background: Several studies have found that DNA methylation is associated with transcriptional regulation and affect sponge regulation of non-coding RNAs in cancer. The integration of circRNA, miRNA, DNA methylation and gene expression data to identify sponge circRNAs is important for revealing the role of DNA methylation-mediated regulation of sponge circRNAs in cancer progression. Method: We established a DNA methylation-mediated circRNA crosstalk network by integrating gene expression, DNA methylation and non-coding RNA data of breast cancer in TCGA. Four modules (26 candidate circRNAs) were mined. Next, 10 DNA methylation-mediated sponge circRNAs (sp_circRNAs) and 5 sponge driver genes (sp_driver genes) in breast cancer were identified in the CMD network using a computational process. Findings: Among the identified genes, ERBB2 was associated with six sponge circRNAs, which illustrates its better sponge regulatory function. Survival analysis showed that DNA methylations of 10 sponge circRNA host genes are potential prognostic biomarkers in the TCGA dataset (p=0.0239) and GSE78754 dataset (p=0.0377). In addition, the DNA methylation of two sponge circRNA host genes showed a significant negative correlation with their driver gene expressions. Interpretation: We developed a strategy to predict sponge circRNAs by DNA methylation mediated with playing the role of regulating breast cancer sponge driver genes. Funding Statement: This work was supported by National Natural Science Foundation of China [grant number 81573021], the Natural Science Foundation of Heilongjiang Province [grant number ZD2015003], and the Heilongjiang Science and Technology Plan Project [YS17C22]. Declaration of Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and company that could be construed as influencing the position presented in, or the review of, this manuscript. Ethics Approval Statement: The authors declare: "Not applicable."