Construction and Investigation of circRNA-associated ceRNA Regulatory Network in Molecular Subtypes of Breast Cancer

Background: Circular RNAs (circRNAs) act as competing endogenous RNAs (ceRNAs) that indirectly regulate gene expression and function by binding microRNAs ( miRNAs). A growing body of evidence indicates that the ceRNA networks can be used as an effective method to investigate cancer; however, the construction and analysis of ceRNA networks, especially circRNA-miRNA-mRNA regulatory network, in different subtypes of breast cancer have not been previously performed. Objectives: In the present study, we generated a ceRNA network to explore their roles in two BC subtypes, namely Luminal A and triple negative breast cancer (TNBC). Methods: First, the expression profiles of circRNA, miRNA, and mRNA were downloaded from the GEO database, differentially expressed genes were obtained using GEO2R, and a ceRNA network was constructed based on circRNA-miRNA pairs and miRNA-mRNA pairs, consisted of 10 circRNAs, 25 miRNAs and 39 mRNAs. Further studies of BC subtypes based on TCGA datasets were also performed to validate the effect of a novel ceRNA network. Results and Discussion: Then, the related genes in the regulatory network were analyzed by GO functional annotation and KEGG pathway enrichment. The analysis showed that targeted genes were enriched in 97 GO terms and 25 KEGG pathways, involved in the molecular typing of breast cancer. Meanwhile, Kaplan-Meier analysis revealed that three key genes (MKI67, DEF8, and GFRA1) were significantly associated with BC tumor differentiation and prognosis. Conclusion: The current study provides a potential application of the ceRNA network within BC subtypes and may offer new targets for their diagnosis, therapy and prognosis.