Abstract
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. 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 five sponge driver genes (sp_driver genes) in breast cancer were identified in the CMD network using a computational process. 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. We developed a strategy to predict sponge circRNAs by DNA methylation mediated with playing the role of regulating breast cancer sponge driver genes.
Highlights
Breast cancer is one of the most common malignant tumors in women (Koboldt et al, 2012)
Differential Target Gene Expression and DNA Methylation of circRNA Host Genes and Target Genes in Breast Cancer miRNAs are abundantly present in many organisms and can selectively interact with complementary mRNAs to reduce protein production
DNA methylation of the target genes could separate breast cancer samples and normal samples (Figure 1B). These findings suggest that the differential levels of DNA methylation may impact target gene expression in breast cancer
Summary
Breast cancer is one of the most common malignant tumors in women (Koboldt et al, 2012). The HER2 (encoded by ERBB2) amplification group has achieved great clinical success because HER2 is an effective therapeutic target for breast cancer (Slamon et al, 1987). The current targeted therapy for breast cancer has not been fully and effectively implemented (Ayca and Traina, 2011). Studies have shown that dysregulated gene expression in breast cancer is affected by various genetic and epigenetic factors, including frequent somatic mutations (Nik-Zainal et al, 2016), copy number variations (Nik-Zainal et al, 2016), single nucleotide polymorphisms (SNPs) (Michailidou et al, 2017), non-coding RNA (Iorio et al, 2015), and DNA methylation (Yang et al, 2001). Epigenetic modifications play an important role in the development and progression of cancer (Esteller, 2008)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
