Identification of breast cancer-related circRNAs by analysis of microarray and RNA-sequencing data: An observational study.

Background: An increasing number of studies indicate that circular RNAs (circRNAs) participate in tumorigenesis. The aim of this study was to elucidate the regulatory mechanisms of circRNAs in breast cancer based on the construction of the circRNA-related ceRNA network.

Methods: The expression profiles of circRNAs, miRNAs, and mRNAs were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. A ceRNA network was constructed by Cytoscape. The interactions among proteins were analyzed using the STRING database, and hub genes were extracted using the cytoHubba application. The functions of the differentially expressed mRNAs (DEmRNAs) were analyzed by the Kyoto Encyclopedia of Gene and Genomes (KEGG) and the Gene Ontology (GO) database.

Results: In total, 7 differentially expressed circRNAs (DEcircRNAs), 27 differentially expressed miRNAs (DEmiRNAs), and 102 DEmRNAs were selected for the construction of the ceRNA network of breast cancer. We established a protein-protein interaction network and identified 6 hub genes. Then, a circRNA-miRNA-hub gene regulatory module was established based on 2 DEcircRNAs, 2 DEmiRNAs, and 2 DEmRNAs. GO and KEGG pathway analyses indicated the possible association of DEmRNAs with breast cancer onset and progression.

Conclusions: The circRNA hsa_circ_0000519 is likely critical in the pathogenesis of breast cancer and may serve as a future therapeutic biomarker.