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

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.

Circular RNA ATAD1 is upregulated in acute myeloid leukemia and promotes cancer cell proliferation by downregulating miR‑34b via promoter methylation

“…In the current study, circ-ATAD1 was shown to be a nucleus-specific circRNA. DNA methylation is known to occur in the nucleus ( 28 ), and numerous circRNAs potentially regulate the methylation of miRNAs in association with cancer biology ( 29 , 30 ). Notably, the present study revealed that circ-ATAD1 downregulated miR-34b expression in AML by increasing methylation of the miR-34b gene promoter.…”

Crosstalk between Methylation and ncRNAs in Breast Cancer: Therapeutic and Diagnostic Implications

“…CircRNAs also play essential roles in DNA methylation and m6A modification regulation. Gu et al reported that abnormal DNA methylation of circRNA might lead to the dysfunction of the miRNA sponge, which indirectly affects the expression of miRNA target genes [ 105 ]. In addition, emerging studies have demonstrated the role of circRNA serving as the miRNA sponge in modulating m6A RNA methylation.…”

Emerging roles of circular RNAs in systemic lupus erythematosus

“…Since circRNAs are primarily generated by the back-splicing of pre-mRNAs, their expression is also determined by the transcription levels of pre-mRNAs, which depend on transcription factor activity and epigenetic modifications, such as methylation, acetylation, and ncRNAs. 16 , 17 , 18 , 19 circRNA expression is also modulated by the regulation of circularization, which involves three main hypothetical models: lariat-driven circularization, in which the formation of a lariat structure brings the upstream splice acceptor and downstream donor into close proximity before splicing; intron-pairing-driven circularization, in which the inverted complementary repeat sequences combine into RNA double strands and are subjected to alternative splicing; and RNA binding protein (RBP)-mediated circularization, in which RBPs join the upstream and downstream flanking introns to facilitate pre-mRNA circularization back-splicing ( Figure 1 ). 13 , 20 , 21 , 22 The type of circRNAs generated depends mainly on the elements involved in the three hypothetical models and the splicing pattern.…”