Constructing a circRNA-miRNA-mRNA Network and Identifying Potential Therapeutic Agents for Breast Cancer

Abstract

Background: Circular RNAs (circRNAs) are central regulators for tumour progression. However, their effects are not entirely definitive in breast cancer (BRCA). We determined the potential function and regulation mechanisms of novel circRNAs in BRCA. Methods: Bioinformatics analyses were used to identify novel circRNAs related to BRCA and to construct circRNA -miRNA-mRNA regulatory network. Findings: Seven differentially expressed circRNAs (DECs) were identified from a microarray dataset (GSE101123). miRNA-binding sites of the seven circRNAs were forecasted. Seventeen circRNA-miRNA interactions were identified, including six circRNAs and 15 miRNAs; 2355 miRNA-related target genes and 1608 differentially expressed genes (DEGs) in BRCA were gathered. There were 149 overlapping genes between the set of miRNA target genes and the set of DEGs. A protein-protein interaction (PPI) network was constructed, which was based on the 149 genes. From this PPI network, seven hub genes are determined. The 149 genes were found to connect with several biological processes and pathways related to tumour. Based on these genes, three compounds (proadifen, pyrimethamine, and arachidonic acid) were identified as therapeutic options for BRCA through connectivity map (CMap) analysis. A circRNA-mediated network was constructed in this study. Interpretation: Our understanding of circRNAs helps to further determine the molecular mechanisms of BRCA and to provide new treatment options. Funding: This study was supported by National Natural Science Foundation of China (No. 81471670); the International Cooperative Project of Shaanxi province, China (No. 2016KW-008) and the Key research and development plan, Shaanxi Province, China (2017ZDXM-SF-066). Declaration of Interest: The authors declare that they have no competing financial interests.